Abstract: Provided are a kit or device for detecting lung cancer and a lung cancer detection method. A kit or device for detecting lung cancer the kit or device including a nucleic acid capable of specifically bonding with miRNA in a specimen of a test subject and a method for detecting lung cancer the method including measuring the miRNA in vitro.
The present invention is used for inspection of the presence or absence of diseased to lung cancer in a subject, specific miRNA and specific detection kit or device of lung cancer, including possible binding nucleic acids, and the using the nucleic acid measuring the expression level of the miRNA method for detecting lung cancer, including.
Background technique
[0002]
Lung oxygen is taken up in the body by breathing, they have an important role to discharge the carbon dioxide. Left lung air taken from the mouth and nose trachea, divided bronchus to the left and right through, go to the right lung, spread to the whole in the lungs through the finer tube, and finally oxygen is incorporated into the blood in the alveoli, carbon dioxide is discharged (non-Patent Document 1).
[0003]
When the National Research and Development Institute of the National Cancer Research Center for Cancer Control and Information Center According to the statistics of the site-specific cancer in 2012 in Japan to disclose, lung cancer sufferers number of 107,241 people, that is, 10 people in the male 1 people, in women is a one in 22 people suffering from lung cancer, sufferers number is a cancer site of the third largest. In addition, males are more likely to suffer nearly twice than women. The number of deaths due to lung cancer is up to 71,518 people to fit men and women, the number of deaths is a cancer site in the first place. In addition, the estimated lung cancer sufferers number of the United States of 2014 up to 224,210 people, of which about 159,260 people is to die (Non-Patent Document 1).
[0004]
Lung cancer There are several species tissue type, for small cell lung cancer, which accounts for about 15%, referred to the rest of the tissue type and non-small cell lung cancer. Non-small cell lung cancer In addition, adenocarcinoma, squamous cell carcinoma, is roughly classified into three large cell carcinoma. These tissue types, the occurrence site, progressive format and speed, etc. are significantly different for the symptoms, also different treatment.
[0005]
The degree of progress of the lung cancer, tumors spread (T0, is, 1 ~ 4), lymph node metastasis (N0 ~ 3), depending on the degree of distant metastasis (M0, M1), is classified as stage 0 to 4. Especially for the spread of the tumor, T1 is what the maximum diameter of the tumor is of 3cm or less, T2 is one more than 3cm but of 7cm below, T3 is what is observed infiltrating the adjacent site or more than 7cm, T4 in size indicate the intended to cover the invasion to a wider adjacent site regardless.
[0006]
The survival rate of lung cancer is different by the degree of progress. According to Non-Patent Document 1, 5-year relative survival rate of non-small cell lung cancer in stage 1 45-49%, Stage 2 30-31%, in the stage 3 5 ~ 14% is reported as 1% for Stage 4 ing. Accordingly, to discover lung cancer at an early stage, greatly contributes to the improvement of survival if possible therapy.
[0007]
Treatment of lung cancer is carried out in the center resection surgery, radiation therapy, an anti-cancer agent treatment. In particular surgery allows adaptation at an early lung cancer is likely to cure (Non-Patent Document 1). In addition, if the early stage of lung cancer, treatment options and some exist, for example thoracoscopic surgery, the trunk stereotactic radiation therapy (SBRT), photodynamic therapy, laser therapy, and brachytherapy is irradiated with radiation from the body treatment like, it may be possible to adapt the burden is small therapy to a patient (non-Patent Document 1).
[0008]
As described in Non-Patent Document 1, the test for lung cancer, in addition to the history surveys and physical examination, is the most prevalent of which is a chest X-ray examination. If the findings there is a doubt in the chest X-ray examination came out, to implement more precise CT examination, MRI examination, diagnostic imaging, such as PET examination. In addition, as a test using a specimen, sputum cytology, pleural effusion examination, stab the needle into the lesion were collected cells and tissues there is a pathological examination examine under a microscope. In addition, as a tumor marker for lung cancer detection is known CEA and CYFRA21-1.
[0009]
Albeit at the research stage, as shown in Patent Documents 1 and 2, the expression level of a micro RNA in a biological sample, including blood (miRNA), or the expression level of the expression level and other protein markers of miRNA by combining, there is a report that to detect lung cancer.
[0010]
Method of detecting lung cancer and other lung diseases using such miR-19 b in the serum (miR-19b-3p) are shown in US Pat.
[0011]
Patent Document 2 has been shown a method of detecting lung cancer using the miR-1268 and miR-1228 in serum or plasma.
[0012]
It has been shown a method of detecting lung cancer by using a miR-1307 blood cell Patent Document 3.
CITATION
Patent literature
[0013]
Patent Document 1: Kohyo 2013-502931 JP
Patent Document 2: WO 2011/146937
Patent Document 3: US Patent Application Publication No. 13/376281 Pat.
Non-patent literature
[0014]
非特許文献1 : American Cancer Society「Lung Cancer(Non-Small Cell)」、2013年監修、p.2~7、37~56
非特許文献2 : Sobin,L.ら、「TNM Classification of Malignant Tumours 第7版」2010年、p.129-134
非特許文献3 : Okamura,K.ら、Lung Cancer、2013年、第80(1)巻、p.45-9
Summary of the invention
Problems that the Invention is to Solve
[0015]
An object of the present invention is to find a novel lung tumor marker, is to provide a method capable of effectively detecting lung cancer using a specific bindable nucleic acid the marker. But as a test of lung cancer is becoming popular is the chest X-ray examination, the number of deaths due to lung cancer is increasing year by year, from the fact that another cancer site the number of deaths is the # 1, X-ray inspection is lung cancer not be necessarily to say that to suppress. Moreover, CT examination or MRI examination, although it is possible to detect lung cancer in high-performance, requires a special apparatus, since the inspection costs are expensive, is not suitable to spread widely as a primary test .
[0016]
The blood tumor markers for lung cancer detection, for example, but such as CEA and CYFRA21-1 is known (Non-Patent Document 3), its usefulness has not been established, the American Cancer Society of lung cancer no description about these markers to guide (non-Patent Document 1). According to Non-Patent Document 3, a typical lung cancer detection sensitivity of these blood tumor markers, CEA is reported 69%, and 43% for CYFRA 21-1. Furthermore, CEA, tumor markers, such as CYFRA 21-1, because it can be increased even for reasons other than lung cancer, determining the presence or absence of lung cancer are said to not be. And it ends up diagnosed with lung cancer by mistake the other cancers, or missed the opportunity of appropriate treatment, wrong unnecessary economic to the patient in applying the medical, will be forced to physically burden.
[0017]
Although it is a research stage, but reported that determines lung cancer using the expression level of a micro RNA (miRNA) in the biological sample, including blood in the following, not put to practical use.
[0018]
Method of detecting lung cancer and other lung diseases using such miR-19 b in the serum (miR-19b-3p) are shown in US Pat. However, since the number of specimens of healthy body used as a negative control is small and ten cases, difficult to say that the universality of the markers for the difference between subjects is secured, unreliable as a method for detecting lung cancer .
[0019]
Patent Document 2, a method to detect lung cancer by using the miR-1268 and miR-1228 in serum and plasma are shown, as are cancers other than lung cancer by examining only mesothelioma three cases he not, cancers other than lung cancer also can not exclude the possibility that a high marker of false positives will be detected.
[0020]
Patent Document 3, a method of detecting lung cancer using a miR-1307 in blood cells of the blood cells have been shown, another case independent and the resulting marker using one case group since it is not verified by the group, unreliable as a means to verify the lung.
[0021]
In this way, in the detection of lung cancer, either because the existing tumor markers that performance is low, also the method of performance and detection for the marker of the research stage is not indicated specifically, in the case of using these, healthy body implementation and wasteful additional testing due to the erroneous detection and lung cancer patients, there is a possibility that the loss occurs in the therapeutic opportunity by overlooking a lung cancer patient. Further, since it is increasing the inspection costs of measuring miRNA consisting of several tens to several hundreds, difficult to use for large-scale screening, such as medical examination. In addition, in order to collect the lung tissue in order to measure the tumor marker is highly undesirable invasive to the patient, can be detected from blood that can be collected in a minimally invasive, the lung cancer patients and lung cancer patients, a healthy body correctly can be identified as a healthy body, high lung cancer marker of accuracy is required. In particular, lung cancer when detected early, a large possibility of surgery, the survival rate can be greatly improved. Also early lung cancer There are several treatment options, such as thoracoscopic surgery or the trunk stereotactic radiation therapy, there is a possibility that can be adapted patient to reduce the burden treatment, high sensitivity that can be detected with a low degree of progression of lung cancer lung cancer markers have been longing.
Means for Solving the Problems
[0022]
The present inventors have result of intensive studies to solve the above problems, found a plurality of genes are available from blood can be collected in less invasive to the detection marker of lung cancer, which in the use of the specifically bindable nucleic acid Accordingly, it found that can significantly detect lung, and completed the present invention.
[0023]
In other words, the present invention has the following features.
(1) is a lung cancer marker, miR-6768-5p, miR-6836-3p , miR-6782-5p, miR-3663-3p, miR-1908-3p, miR-6726-5p, miR-4258, miR- 1343-3p, miR-4516, miR- 6875-5p, miR-4651, miR-6825-5p, miR-6840-3p, miR-6780b-5p, miR-6749-5p, miR-8063, miR-6784- 5p, miR-3679-5p, miR- 3184-5p, miR-663b, miR-6880-5p, miR-1908-5p, miR-92a-2-5p, miR-7975, miR-7110-5p, miR- 6842-5p, miR-6857-5p, miR- 5572, miR-3197, miR-6131, miR-6889-5p, miR-4454, miR-1199-5p, miR-1247-3p, miR-6800-5p, miR-6872-3p, miR-4649-5p, miR-6791-5p, miR-4433b-3p, miR-3135b, miR-128-2-5p, miR-4675, miR-4472, miR-6785-5p, miR-6741-5p, miR-7977, miR-3665, miR-128-1-5p, miR-4286, miR-6765-3p, miR-4632-5p, miR-365a-5p, miR-6088, miR- 6816-5p, miR-6885-5p, miR- 711, miR-6765-5p, miR-3180, miR-4442, miR-4792, miR-6721-5p, miR-6798-5p, miR-3162-5p, miR-6126, miR-4758-5p, miR-2392, miR-486-3p, miR-6727-5p, miR-4728-5p, miR-6746-5p, miR-4270, miR-3940-5p, miR- 4725-3p, miR-7108-5p, miR- 3656, miR-6879-5p, miR-6738-5p, miR-1260a, miR-4446-3p, miR-3131, miR-4463, miR-3185, miR- 6870-5p, miR-6779-5p, miR- 1273g-3p, miR-8059, miR-4697-5p, miR-4674, miR-4433-3p, miR-4257, miR-1915-5p, miR-4417, miR-1343-5p, miR-6781-5p, miR-4695-5p, miR-1237-5p, miR-6775-5p, miR-7845-5p, miR-4746-3p, miR-7641, miR-7847- 3p, miR-6806-5p, miR- 4467, miR-4726-5p, miR-4648, miR-6089, miR-1260b, miR-4532, miR-5195-3p, miR-3188, miR-6848-5p, miR-1233-5p, miR-6717-5p, miR-3195, miR-6757-5p, miR-8072, miR-4745-5p, miR-6511a-5p, miR-6776-5p, miR-371a-5p, miR-1227-5p, miR-7150, miR-1915-3p, miR-187-5p, miR-614, miR-1225-5p, miR-451a, miR-939-5p, miR-223-3p, miR- 125a-3p, miR-92b- 5p, miR-22-3p, miR-6073, miR-6845-5p, miR-6769b-5p, miR-4665-3p, miR-1913, miR-1228-3p, miR- 940, miR-296-3p, miR- 4690-5p, miR-548q, miR-663a, miR-1249, miR-1202, miR-7113-3p, miR-1225-3p, miR-4783-3p, miR- 4448 and at least one or more poly comprising nucleotides capable of specifically bound nucleic acid, a kit for detecting lung cancer selected from the group consisting of miR-4534.
[0024]
(2) miR-6768-5p is hsa-miR-6768-5p, miR-6836-3p is hsa-miR-6836-3p, miR-6782-5p is located in the hsa-miR-6782-5p , miR-3663-3p is hsa-miR-3663-3p, miR-1908-3p is hsa-miR-1908-3p, miR-6726-5p is hsa-miR-6726-5p, miR -4258 is hsa-miR-4258, miR-1343-3p is hsa-miR-1343-3p, miR-4516 is hsa-miR-4516, miR-6875-5p is hsa-miR-6875 a -5p, miR-4651 is hsa-miR-4651, miR-6825-5p is hsa-miR-6825-5p, miR-6840-3p is hsa-miR-6840-3p, miR -6780b-5p is hsa-miR-6780b-5p, miR-6749-5p is hsa-miR-6749-5p, miR-8063 is hsa-miR-8063, miR-6784-5p is hsa -miR-6784-5p is, miR-3679-5p is hsa-miR-3679-5p, miR-3184-5p is hsa-miR-3184-5p, miR-663b is hsa-miR-663b at is, miR-6880-5p is hsa-miR-6880-5p, miR-1908-5p is hsa-miR-1908-5p, miR-92a-2-5p is hsa-miR-92a-2 a -5p, miR-7975 is hsa-miR-7975, miR-7110-5p is hsa-miR-7110-5p, miR-6842-5p is hsa-miR-6842-5p, miR -6857-5p is hsa-miR-6857-5p, miR-5572 is hsa-miR-5572, miR-3197 is hsa-miR-3197, miR-6131 is located in the hsa-miR-6131 , miR-6889-5p is hsa-miR-6889-5p, miR-4454 is hsa-miR-4454, miR-1199-5p is hsa-miR-1199-5p, miR-1247-3p there is a hsa-miR-1247-3p, miR-6800-5p is hsa-miR-6800-5p, miR-6872-3p is hsa-miR-6872-3p, miR-4649-5p is hsa -miR-4649-5p is, miR-6791-5p is hsa-miR-6791-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-3135b is hsa-miR-3135b at is, miR-128-2-5p is hsa-miR-128-2-5p, miR-4675 is hsa-miR-4675, miR-4472 is hsa-miR-4472, miR-6785 -5p is hsa-miR-6785-5p, miR-6741-5p is hsa-miR-6741-5p, miR-7977 is hsa-miR-7977, miR-3665 is hsa-miR-3665 at is, miR-128-1-5p is hsa-miR-128-1-5p, miR-4286 is hsa-miR-4286, miR-6765-3p is located in the hsa-miR-6765-3p , miR-4632-5p is hsa-miR-4632-5p, miR-365a-5p is hsa-miR-365a-5p, miR-6088 is hsa-miR-6088, miR-6816-5p there is a hsa-miR-6816-5p, miR-6885-5p is hsa-miR-6885-5p, miR-711 is hsa-miR-711, miR-6765-5p is hsa-miR-6765 a -5p, miR-3180 is hsa-miR-3180, miR-4442 is hsa-miR-4442, miR-4792 is hsa-miR-4792, miR-6721-5p is hsa-miR a -6721-5p, miR-6798-5p is hsa-miR-6798-5p, miR-3162-5p is hsa-miR-3162-5p, miR-6126 is located in the hsa-miR-6126 , miR-4758-5p is hsa-miR-4758-5p, miR-2392 is hsa-miR-2392, miR-486-3p is hsa-miR-486-3p, miR-6727-5p there is a hsa-miR-6727-5p, miR-4728-5p is hsa-miR-4728-5p, miR-6746-5p is hsa-miR-6746-5p, miR-4270 is hsa-miR is -4270, miR-3940-5p is hsa-miR-3940-5p, miR-4725-3p is hsa-miR-4725-3p, miR-7108-5p is hsa-miR-7108-5p at is, miR-3656 is hsa-miR-3656, miR-6879-5p is hsa-miR-6879-5p, miR-6738-5p is hsa-miR-6738-5p, miR-1260a there is a hsa-miR-1260a, miR-4446-3p is hsa-miR-4446-3p, miR-3131 is hsa-miR-3131, miR-4463 is hsa-miR-4463, miR -3185 is hsa-miR-3185, miR-6870-5p is hsa-miR-6870-5p, miR-6779-5p is hsa-miR-6779-5p, the miR-1273g-3p hsa a -miR-1273g-3p, miR-8059 is hsa-miR-8059, miR-4697-5p is hsa-miR-4697-5p, miR-4674 is hsa-miR-4674, miR -4433-3p is hsa-miR-4433-3p, miR-4257 is hsa-miR-4257, miR-1915-5p is hsa-miR-1915-5p, miR-4417 is hsa-miR is -4417, miR-1343-5p is hsa-miR-1343-5p, miR-6781-5p is hsa-miR-6781-5p, miR-4695-5p is hsa-miR-4695-5p at is, miR-1237-5p is hsa-miR-1237-5p, miR-6775-5p is hsa-miR-6775-5p, miR-7845-5p is located in the hsa-miR-7845-5p , miR-4746-3p is hsa-miR-4746-3p, miR-7641 is hsa-miR-7641, miR-7847-3p is hsa-miR-7847-3p, miR-6806-5p There is a hsa-miR-6806-5p, miR-4467 is hsa-miR-4467, miR-4726-5p is hsa-miR-4726-5p, miR-4648 is located in the hsa-miR-4648 , miR-6089 is hsa-miR-6089, miR-1260b is hsa-miR-1260b, miR-4532 is hsa-miR-4532, miR-5195-3p is hsa-miR-5195-3p at is, miR-3188 is hsa-miR-3188, miR-6848-5p is hsa-miR-6848-5p, miR-1233-5p is hsa-miR-1233-5p, miR-6717 -5p is hsa-miR-6717-5p, miR-3195 is hsa-miR-3195, miR-6757-5p is hsa-miR-6757-5p, miR-8072 is hsa-miR-8072 at is, miR-4745-5p is hsa-miR-4745-5p, miR-6511a-5p is hsa-miR-6511a-5p, miR-6776-5p is located in the hsa-miR-6776-5p , miR-371a-5p is hsa-miR-371a-5p, miR-1227-5p is hsa-miR-1227-5p, miR-7150 is hsa-miR-7150, miR-1915-3p there hsa-miR-1915-3p, miR-187-5p is hsa-miR-187-5p, miR-614 is hsa-miR-614, miR-1225-5p is hsa-miR-1225-5p at is, miR-451a is hsa-miR-451a, miR-939-5p is hsa-miR-939-5p, miR-223-3p is hsa-miR-223-3p, miR-125a -3p is hsa-miR-125a-3p, miR-92b-5p is hsa-miR-92b-5p, miR-22-3p is hsa-miR-22-3p, the miR-6073 hsa -miR-6073 and is, miR-6845-5p is hsa-miR-6845-5p, miR-6769b-5p is hsa-miR-6769b-5p, miR-4665-3p is hsa-miR-4665 a -3p, miR-1913 is hsa-miR-1913, miR-1228-3p is hsa-miR-1228-3p, miR-940 is hsa-miR-940, miR-296-3p There is a hsa-miR-296-3p, miR-4690-5p is hsa-miR-4690-5p, miR-548q is hsa-miR-548q, miR-663a is located in the hsa-miR-663a , miR-1249 is hsa-miR-1249, miR-1202 is hsa-miR-1202, miR-7113-3p is hsa-miR-7113-3p, miR-1225-3p is hsa-miR a -1225-3p, miR-4783-3p is hsa-miR-4783-3p, miR-4448 is hsa-miR-4448, and, miR-4534 is hsa-miR-4534, ( the kit according to 1).
[0025]
(3) said nucleic acid, a polynucleotide shown in the following (a) -
(e): represented by any one of (a) SEQ ID NO: 1 ~ 125, 127 ~ 130, 132 ~ 134, and, 561-578 polynucleotides, a variant thereof u in the nucleotide sequence or the nucleotide sequence consisting of a nucleotide sequence which is t, the fragment comprising the derivative, or 15 or more contiguous
bases, (b) SEQ ID NO: 1 ~ 125 127 ~ 130 , 132-134, and a polynucleotide comprising the nucleotide sequence represented by any one of
561-578, (c) SEQ ID NOs 125 and 127 ~ 130, 132 ~ 134, and, in one of 561-578 polynucleotides u in the nucleotide sequence or the nucleotide sequence represented consists of a nucleotide sequence complementary to the nucleotide sequence which is t, the fragment comprising the variant, derivative, or 15 or more contiguous bases,
(d-) SEQ ID NO: 1 ~ 125, 127 ~ 130, 132 ~ 134, and a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of 561-578 and
(e) above (a) ~ any polynucleotide under stringent hybridizing polynucleotides under conditions of (d-),
a polynucleotide selected from the group consisting of, (1) or (2) the kit according to.
[0026]
(4) the kit is another lung markers, miR-19b-3p, at least one or more polynucleotides that specifically bind to selected from the group consisting of miR-1228-5p and miR-1307-3p possible further comprises a nucleic acid, the kit according to any one of (1) to (3).
[0027]
(5) miR-19b-3p is hsa-miR-19b-3p, miR-1228-5p is hsa-miR-1228-5p, and, miR-1307-3p is hsa-miR-1307-3p in a kit according to (4).
[0028]
(6) a nucleic acid is poly shown in the following (f) ~ (j)
nucleotides: u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (f) SEQ ID NO: 126 and 131 and 579 polynucleotides, a variant thereof consisting of the nucleotide sequence, a derivative, or a fragment comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (g) SEQ ID NO: 126 and 131 and 579,
(h) SEQ ID NO: 126 and 131 and 579 or u in the nucleotide sequence or the nucleotide sequence represented by consists of a nucleotide sequence complementary to the nucleotide sequence is t polynucleotide, its variants, derivatives thereof, or a fragment thereof comprising 15 or more contiguous bases,
comprising nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (i) SEQ ID NO: 126 and 131 and 579 polynucleotides, and
(j) wherein (f) ~ any polynucleotide and a polynucleotide hybridizing under stringent conditions (i), a polynucleotide selected from the group consisting of, (4) or ( the kit according to 5).
[0029]
(7) The kit is another of lung cancer markers, miR-4271, miR-642b-3p, miR-6075, miR-6125, miR-887-3p, miR-6851-5p, miR-6763-5p, miR-3928-3p, miR-4443, miR-3648, miR-149-3p, miR-4689, miR-4763-3p, miR-6729-5p, miR-3196, miR-8069, miR-1268a, miR- 4739, miR-1268b, miR-5698, miR-6752-5p, miR-4507, miR-564, miR-4497, miR-6877-5p, miR-6087, miR-4731-5p, miR-615-5p, miR-760, miR-6891-5p, miR-6887-5p, miR-4525, miR-1914-3p, miR-619-5p, miR-5001-5p, miR-6722-3p, miR-3621, miR- 4298, further comprising the miR-675-5p and at least one polynucleotide capable of specifically bound nucleic acid is selected from the group consisting of miR-4655-5p, under any of (1) to (6) the kit according.
[0030]
(8) miR-4271 is hsa-miR-4271, miR-642b-3p is hsa-miR-642b-3p, miR-6075 is hsa-miR-6075, miR-6125 is hsa-miR is -6125, miR-887-3p is hsa-miR-887-3p, miR-6851-5p is hsa-miR-6851-5p, miR-6763-5p is hsa-miR-6763-5p at is, miR-3928-3p is hsa-miR-3928-3p, miR-4443 is hsa-miR-4443, miR-3648 is hsa-miR-3648, miR-149-3p is hsa -miR-149-3p is, miR-4689 is hsa-miR-4689, miR-4763-3p is hsa-miR-4763-3p, miR-6729-5p is hsa-miR-6729-5p at is, miR-3196 is hsa-miR-3196, miR-8069 is hsa-miR-8069, miR-1268a is hsa-miR-1268a, miR-4739 is located in the hsa-miR-4739 , miR-1268b is hsa-miR-1268b, miR-5698 is hsa-miR-5698, miR-6752-5p is hsa-miR-6752-5p, miR-4507 is hsa-miR-4507 at is, miR-564 is hsa-miR-564, miR-4497 is hsa-miR-4497, miR-6877-5p is hsa-miR-6877-5p, miR-6087 is hsa-miR is -6087, miR-4731-5p is hsa-miR-4731-5p, miR-615-5p is hsa-miR-615-5p, miR-760 is hsa-miR-760, miR -6891-5p is hsa-miR-6891-5p, miR-6887-5p is hsa-miR-6887-5p, miR-4525 is hsa-miR-4525, miR-1914-3p is hsa a -miR-1914-3p, miR-619-5p is hsa-miR-619-5p, miR-5001-5p is hsa-miR-5001-5p, miR-6722-3p is hsa-miR a -6722-3p, miR-3621 is hsa-miR-3621, miR-4298 is hsa-miR-4298, miR-675-5p is hsa-miR-675-5p, and, miR -4655-5p is hsa-miR-4655-5p, kit according to (7).
[0031]
(9) said nucleic acid, the following (k) ~ (o) are shown
polynucleotide: (k) the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 135-174 polynucleotide consisting, variants, derivatives thereof, or a fragment comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any of (l) SEQ ID NO: 135 ~ 174,
(yd) sequence No. 135 polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of 174, a variant, derivative, or 15 or more contiguous bases a fragment containing the
polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence that u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 135-174, and
(o) the (k) any of the polynucleotides under stringent conditions with a polynucleotide hybridizing of ~ (n),
is a polynucleotide selected from the group consisting of a kit according to (7) or (8).
[0032]
(10) The kit of (1) or (2) respectively and capable of specifically binding at least two nucleic acids of at least two polynucleotides selected from the group consisting of all lung markers described the containing, kit according to any one of (1) to (9).
[0033]
(11) 肺 が ん マ ー カ ー で あ る, miR-6768-5p, miR-6836-3p, miR-6782-5p, miR-3663-3p, miR-1908-3p, miR-6726-5p, miR-4258, miR 1343-3p, miR-4516, miR-6875-5p, miR-4651, miR-6825-5p, miR-6840-3p, miR-6780b-5p, miR-6749-5p, miR-8063, miR-6784- 5p, miR-3679-5p, miR-3184-5p, miR-663b, miR-6880-5p, miR-1908-5p, miR-92a-2-5p, miR-7975, miR-7110-5p, miR 6842-5p, miR-6857-5p, miR-5572, miR-3197, miR-6131, miR-6889-5p, miR-4454, miR-1199-5p, miR-1247-3p, miR-6800-5p, miR-6872-3p, miR-4649-5p, miR-6791-5p, miR-4433b-3p, miR-3135b, miR-128-2-5p, miR-4675, miR-4472, miR-6785-5p, miR-6741-5p, miR-7977, miR-3665, miR-128-1-5p, miR-4286, miR-6765-3p, miR-4632-5p, miR-365a-5p, miR-6088, miR 6816-5p, miR-6885-5p, miR-711, miR-6765-5p, miR-3180, miR-4442, miR-4792, miR-6721-5p, miR-6798-5p, miR-3162-5p, miR-6126, miR-4758-5p, miR-2392, miR-486-3p, miR-6727-5p, miR-4728-5p, miR-6746-5p, miR-4270, miR-3940-5p, miR 4725-3p, miR-7108-5p, miR-3656, miR-6879-5p, miR-6738-5p, miR-1260a, miR-4446-3p, miR-3131, miR-4463, miR-3185, miR 6870-5p, miR-6779-5p, miR-1273g-3p, miR-8059, miR-4697-5p, miR-4674, miR-4433-3p, miR-4257, miR-1915-5p, miR-4417, miR-1343-5p, miR-6781-5p, miR-4695-5p, miR-1237-5p, miR-6775-5p, miR-7845-5p, miR-4746-3p, miR-7641, miR-7847- 3p, miR-6806-5p, miR-4467, miR-4726-5p, miR-4648, miR-6089, miR-1260b, miR-4532, miR-5195-3p, miR-3188, miR-6848-5p, miR-1233-5p, miR-6717-5p, miR-3195, miR-6757-5p, miR-8072, miR-4745-5p, miR-6511a-5p, miR-6776-5p, miR-371a-5p, miR-1227-5p, miR-7150, miR-1915-3p, miR-187-5p, miR-614, miR-1225-5p, miR-451a, miR-939-5p, miR-223-3p, miR 125a-3p, miR-92b-5p, miR-22-3p, miR-6073, miR-6845-5p, miR-6769b-5p, miR-4665-3p, miR-1913, miR-1228-3p, miR 940, miR-296-3p, miR-4690-5p, miR-548q, miR-663a, miR-1249, miR-1202, miR-7113-3p, miR-1225-3p, miR-4783-3p, miR 4448 及 び miR-4534 か ら な る 群 か ら 選 択 さ れ る 少 な く と も 1 つ 以上 の ポ リ ヌ ク レ オ チ ド と 特異 的 に 結合 可能 な 核酸 を 含 む, 肺 が ん の 検 出 用 デ バ イ ス.
[0034]
(12) miR-6768-5p is hsa-miR-6768-5p, miR-6836-3p is hsa-miR-6836-3p, miR-6782-5p is located in the hsa-miR-6782-5p , miR-3663-3p is hsa-miR-3663-3p, miR-1908-3p is hsa-miR-1908-3p, miR-6726-5p is hsa-miR-6726-5p, miR -4258 is hsa-miR-4258, miR-1343-3p is hsa-miR-1343-3p, miR-4516 is hsa-miR-4516, miR-6875-5p is hsa-miR-6875 a -5p, miR-4651 is hsa-miR-4651, miR-6825-5p is hsa-miR-6825-5p, miR-6840-3p is hsa-miR-6840-3p, miR -6780b-5p is hsa-miR-6780b-5p, miR-6749-5p is hsa-miR-6749-5p, miR-8063 is hsa-miR-8063, miR-6784-5p is hsa -miR-6784-5p is, miR-3679-5p is hsa-miR-3679-5p, miR-3184-5p is hsa-miR-3184-5p, miR-663b is hsa-miR-663b at is, miR-6880-5p is hsa-miR-6880-5p, miR-1908-5p is hsa-miR-1908-5p, miR-92a-2-5p is hsa-miR-92a-2 a -5p, miR-7975 is hsa-miR-7975, miR-7110-5p is hsa-miR-7110-5p, miR-6842-5p is hsa-miR-6842-5p, miR -6857-5p is hsa-miR-6857-5p, miR-5572 is hsa-miR-5572, miR-3197 is hsa-miR-3197, miR-6131 is located in the hsa-miR-6131 , miR-6889-5p is hsa-miR-6889-5p, miR-4454 is hsa-miR-4454, miR-1199-5p is hsa-miR-1199-5p, miR-1247-3p there is a hsa-miR-1247-3p, miR-6800-5p is hsa-miR-6800-5p, miR-6872-3p is hsa-miR-6872-3p, miR-4649-5p is hsa -miR-4649-5p is, miR-6791-5p is hsa-miR-6791-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-3135b is hsa-miR-3135b at is, miR-128-2-5p is hsa-miR-128-2-5p, miR-4675 is hsa-miR-4675, miR-4472 is hsa-miR-4472, miR-6785 -5p is hsa-miR-6785-5p, miR-6741-5p is hsa-miR-6741-5p, miR-7977 is hsa-miR-7977, miR-3665 is hsa-miR-3665 at is, miR-128-1-5p is hsa-miR-128-1-5p, miR-4286 is hsa-miR-4286, miR-6765-3p is located in the hsa-miR-6765-3p , miR-4632-5p is hsa-miR-4632-5p, miR-365a-5p is hsa-miR-365a-5p, miR-6088 is hsa-miR-6088, miR-6816-5p there is a hsa-miR-6816-5p, miR-6885-5p is hsa-miR-6885-5p, miR-711 is hsa-miR-711, miR-6765-5p is hsa-miR-6765 a -5p, miR-3180 is hsa-miR-3180, miR-4442 is hsa-miR-4442, miR-4792 is hsa-miR-4792, miR-6721-5p is hsa-miR a -6721-5p, miR-6798-5p is hsa-miR-6798-5p, miR-3162-5p is hsa-miR-3162-5p, miR-6126 is located in the hsa-miR-6126 , miR-4758-5p is hsa-miR-4758-5p, miR-2392 is hsa-miR-2392, miR-486-3p is hsa-miR-486-3p, miR-6727-5p there is a hsa-miR-6727-5p, miR-4728-5p is hsa-miR-4728-5p, miR-6746-5p is hsa-miR-6746-5p, miR-4270 is hsa-miR is -4270, miR-3940-5p is hsa-miR-3940-5p, miR-4725-3p is hsa-miR-4725-3p, miR-7108-5p is hsa-miR-7108-5p at is, miR-3656 is hsa-miR-3656, miR-6879-5p is hsa-miR-6879-5p, miR-6738-5p is hsa-miR-6738-5p, miR-1260a there is a hsa-miR-1260a, miR-4446-3p is hsa-miR-4446-3p, miR-3131 is hsa-miR-3131, miR-4463 is hsa-miR-4463, miR -3185 is hsa-miR-3185, miR-6870-5p is hsa-miR-6870-5p, miR-6779-5p is hsa-miR-6779-5p, the miR-1273g-3p hsa a -miR-1273g-3p, miR-8059 is hsa-miR-8059, miR-4697-5p is hsa-miR-4697-5p, miR-4674 is hsa-miR-4674, miR -4433-3p is hsa-miR-4433-3p, miR-4257 is hsa-miR-4257, miR-1915-5p is hsa-miR-1915-5p, miR-4417 is hsa-miR is -4417, miR-1343-5p is hsa-miR-1343-5p, miR-6781-5p is hsa-miR-6781-5p, miR-4695-5p is hsa-miR-4695-5p at is, miR-1237-5p is hsa-miR-1237-5p, miR-6775-5p is hsa-miR-6775-5p, miR-7845-5p is located in the hsa-miR-7845-5p , miR-4746-3p is hsa-miR-4746-3p, miR-7641 is hsa-miR-7641, miR-7847-3p is hsa-miR-7847-3p, miR-6806-5p There is a hsa-miR-6806-5p, miR-4467 is hsa-miR-4467, miR-4726-5p is hsa-miR-4726-5p, miR-4648 is located in the hsa-miR-4648 , miR-6089 is hsa-miR-6089, miR-1260b is hsa-miR-1260b, miR-4532 is hsa-miR-4532, miR-5195-3p is hsa-miR-5195-3p at is, miR-3188 is hsa-miR-3188, miR-6848-5p is hsa-miR-6848-5p, miR-1233-5p is hsa-miR-1233-5p, miR-6717 -5p is hsa-miR-6717-5p, miR-3195 is hsa-miR-3195, miR-6757-5p is hsa-miR-6757-5p, miR-8072 is hsa-miR-8072 at is, miR-4745-5p is hsa-miR-4745-5p, miR-6511a-5p is hsa-miR-6511a-5p, miR-6776-5p is located in the hsa-miR-6776-5p , miR-371a-5p is hsa-miR-371a-5p, miR-1227-5p is hsa-miR-1227-5p, miR-7150 is hsa-miR-7150, miR-1915-3p there hsa-miR-1915-3p, miR-187-5p is hsa-miR-187-5p, miR-614 is hsa-miR-614, miR-1225-5p is hsa-miR-1225-5p at is, miR-451a is hsa-miR-451a, miR-939-5p is hsa-miR-939-5p, miR-223-3p is hsa-miR-223-3p, miR-125a -3p is hsa-miR-125a-3p, miR-92b-5p is hsa-miR-92b-5p, miR-22-3p is hsa-miR-22-3p, the miR-6073 hsa -miR-6073 and is, miR-6845-5p is hsa-miR-6845-5p, miR-6769b-5p is hsa-miR-6769b-5p, miR-4665-3p is hsa-miR-4665 a -3p, miR-1913 is hsa-miR-1913, miR-1228-3p is hsa-miR-1228-3p, miR-940 is hsa-miR-940, miR-296-3p There is a hsa-miR-296-3p, miR-4690-5p is hsa-miR-4690-5p, miR-548q is hsa-miR-548q, miR-663a is located in the hsa-miR-663a , miR-1249 is hsa-miR-1249, miR-1202 is hsa-miR-1202, miR-7113-3p is hsa-miR-7113-3p, miR-1225-3p is hsa-miR a -1225-3p, miR-4783-3p is hsa-miR-4783-3p, miR-4448 is hsa-miR-4448, and, miR-4534 is hsa-miR-4534, ( a device according to 11).
[0035]
(13) said nucleic acid, a polynucleotide shown in the following (a) -
(e): represented by any one of (a) SEQ ID NO: 1 ~ 125, 127 ~ 130, 132 ~ 134, and, 561-578 polynucleotides, a variant thereof u in the nucleotide sequence or the nucleotide sequence consisting of a nucleotide sequence which is t, the fragment comprising the derivative, or 15 or more contiguous
bases, (b) SEQ ID NO: 1 ~ 125 127 ~ 130 , 132-134, and a polynucleotide comprising the nucleotide sequence represented by any one of
561-578, (c) SEQ ID NOs 125 and 127 ~ 130, 132 ~ 134, and, in one of 561-578 polynucleotides u in the nucleotide sequence or the nucleotide sequence represented consists of a nucleotide sequence complementary to the nucleotide sequence which is t, the fragment comprising the variant, derivative, or 15 or more contiguous bases,
(d-) SEQ ID NO: 1 ~ 125, 127 ~ 130, 132 ~ 134, and a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of 561-578 and
(e) any of the polynucleotides and a polynucleotide hybridizing under stringent conditions, the (a) ~ (d-)
a polynucleotide selected from the consisting of group, (11) or (12) a device according to.
[0036]
(14) said device is another lung markers, miR-19b-3p, at least one or more polynucleotides that specifically bind to selected from the group consisting of miR-1228-5p and miR-1307-3p possible further comprises a nucleic acid, the device according to any one of (11) to (13).
[0037]
(15) miR-19b-3p is hsa-miR-19b-3p, miR-1228-5p is hsa-miR-1228-5p, and, miR-1307-3p is hsa-miR-1307-3p at is, the device described in (14).
[0038]
(16) wherein the nucleic acid is poly shown in the following (f) ~ (j)
nucleotides: u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (f) SEQ ID NO: 126 and 131 and 579 polynucleotides, a variant thereof consisting of the nucleotide sequence, a derivative, or a fragment comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any one of (g) SEQ ID NO: 126 and 131 and 579,
(h) SEQ ID NO: 126 and 131 and 579 or u in the nucleotide sequence or the nucleotide sequence represented by consists of a nucleotide sequence complementary to the nucleotide sequence is t polynucleotide, its variants, derivatives thereof, or a fragment thereof comprising 15 or more contiguous bases,
comprising nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (i) SEQ ID NO: 126 and 131 and 579 polynucleotides, and
(j) wherein (f) ~ any polynucleotide and a polynucleotide hybridizing under stringent conditions (i),
a polynucleotide selected from the group consisting of, (14) or ( a device according to 15).
[0039]
(17) The device is another of lung cancer markers, miR-4271, miR-642b-3p, miR-6075, miR-6125, miR-887-3p, miR-6851-5p, miR-6763-5p, miR-3928-3p, miR-4443, miR-3648, miR-149-3p, miR-4689, miR-4763-3p, miR-6729-5p, miR-3196, miR-8069, miR-1268a, miR- 4739, miR-1268b, miR-5698, miR-6752-5p, miR-4507, miR-564, miR-4497, miR-6877-5p, miR-6087, miR-4731-5p, miR-615-5p, miR-760, miR-6891-5p, miR-6887-5p, miR-4525, miR-1914-3p, miR-619-5p, miR-5001-5p, miR-6722-3p, miR-3621, miR- 4298, further comprising the miR-675-5p and at least one polynucleotide capable of specifically bound nucleic acid is selected from the group consisting of miR-4655-5p, to any one of (11) to (16) device described.
[0040]
(18) miR-4271 is hsa-miR-4271, miR-642b-3p is hsa-miR-642b-3p, miR-6075 is hsa-miR-6075, miR-6125 is hsa-miR is -6125, miR-887-3p is hsa-miR-887-3p, miR-6851-5p is hsa-miR-6851-5p, miR-6763-5p is hsa-miR-6763-5p at is, miR-3928-3p is hsa-miR-3928-3p, miR-4443 is hsa-miR-4443, miR-3648 is hsa-miR-3648, miR-149-3p is hsa -miR-149-3p is, miR-4689 is hsa-miR-4689, miR-4763-3p is hsa-miR-4763-3p, miR-6729-5p is hsa-miR-6729-5p at is, miR-3196 is hsa-miR-3196, miR-8069 is hsa-miR-8069, miR-1268a is hsa-miR-1268a, miR-4739 is located in the hsa-miR-4739 , miR-1268b is hsa-miR-1268b, miR-5698 is hsa-miR-5698, miR-6752-5p is hsa-miR-6752-5p, miR-4507 is hsa-miR-4507 at is, miR-564 is hsa-miR-564, miR-4497 is hsa-miR-4497, miR-6877-5p is hsa-miR-6877-5p, miR-6087 is hsa-miR is -6087, miR-4731-5p is hsa-miR-4731-5p, miR-615-5p is hsa-miR-615-5p, miR-760 is hsa-miR-760, miR -6891-5p is hsa-miR-6891-5p, miR-6887-5p is hsa-miR-6887-5p, miR-4525 is hsa-miR-4525, miR-1914-3p is hsa a -miR-1914-3p, miR-619-5p is hsa-miR-619-5p, miR-5001-5p is hsa-miR-5001-5p, miR-6722-3p is hsa-miR a -6722-3p, miR-3621 is hsa-miR-3621, miR-4298 is hsa-miR-4298, miR-675-5p is hsa-miR-675-5p, and, miR -4655-5p is hsa-miR-4655-5p, according to (17) devices.
[0041]
(19) said nucleic acid, the following (k) ~ (o) are shown
polynucleotide: (k) the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 135-174 polynucleotide consisting, variants, derivatives thereof, or a fragment comprising 15 or more continuous nucleotides,
polynucleotides comprising a nucleotide sequence represented by any of (l) SEQ ID NO: 135 ~ 174,
(yd) sequence No. 135 polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of 174, a variant, derivative, or 15 or more contiguous bases a fragment containing the
polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence that u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 135-174, and
(o) the (k) any of the polynucleotides under stringent hybridizing polynucleotides under conditions of ~ (n),
is a polynucleotide selected from the group consisting of, according to (17) or (18) device.
[0042]
(20) wherein the device is a device for measuring by hybridization techniques, according to any one of (11) to (19) device.
[0043]
(21) The hybridization techniques, a nucleic acid array technology, as described in (20) device.
[0044]
(22) wherein the device comprises at least two or more nucleic acids respectively capable of specifically binding at least two or more polynucleotides selected from all lung markers described (11) or (12), device according to any one of (11) to (21).
[0045]
(23) (1) Kit or (11) according to any one of (10) using a device according to any of (22), measuring the expression level of a target nucleic acid in the specimen of a subject, and expression level which is the measurement, by using the control expression level in healthy body that is measured in the same manner that the subject is suffering from lung cancer, or to evaluate the in vitro that not suffering from lung cancer including, a method of detecting lung cancer.
[0046]
(24) wherein the subject is a human, the method described in (23).
[0047]
(25) wherein the analyte is blood, serum or plasma, the method described in (23) or (24).
[0048]
Terms used herein have the following definitions.
[0049]
Nucleotide, polynucleotide, DNA, by abbreviations such as RNA shall be in accordance with customary in the "Guidelines for the creation of specification and the like, including the nucleotide sequence or amino acid sequence" (Japan Patent Office ed.) And the art .
[0050]
A "polynucleotide" as used herein, RNA, DNA, and none of the RNA / DNA (chimeric) used for encompasses nucleic acids. Incidentally, the above-mentioned DNA, include cDNA, genomic DNA, and even synthetic DNA is. Also included in the above RNA, total RNA, include mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, none of the non-coding (non-coding) RNA and synthetic RNA are. "Synthetic DNA" and "synthetic RNA" as used herein based on the predetermined nucleotide sequence (either the native sequence or non-naturally occurring sequence good.), For example using an automated nucleic acid synthesizer, artificially It refers fabricated DNA and RNA. "Non-naturally occurring sequence" as used herein, are intended to be used in the broad sense, differs from the native sequence, for example, one or more nucleotide substitutions, deletions, insertions and / or sequence comprising additional ( that includes mutated sequence), the sequence comprising one or more modified nucleotides (i.e., a modified sequence), and the like. In this description, a polynucleotide is used interchangeably with nucleic acid.
[0051]
The term "fragment" as used herein, is a polynucleotide having a nucleotide sequence of contiguous portion of a polynucleotide, 15 nucleotides or more, it is desirable that preferably 17 bases or more, more preferably having 19 or more bases in length .
[0052]
"Gene" as used herein, RNA, and not double-stranded DNA only, include the single-stranded DNA, such as a plus strand constituting it (or sense strand) or complementary strand (or antisense strand) used is intended to. Also not to be particularly limited by its length.
[0053]
Thus, a "gene", as used herein, unless otherwise stated, a double-stranded DNA, one strand having a single-stranded DNA (plus strand) complementary to sequence the positive strand containing a cDNA containing the human genomic DNA DNA (complementary strand), micro-RNA (miRNA), and their fragments, and none of the transcript contains. Also the "gene" is not only a "gene" represented by a specific nucleotide sequence (or a SEQ ID NO), RNA RNA and biological functions encoded by these are equivalent, for example, homologs (i.e., homologs or orthologs), encompasses genetic variants such as polymorphisms, and "nucleic acid" encoding derivatives. Such homologues, the "nucleic acid" which encodes the variant or derivative, in particular, under stringent conditions as described later, a nucleotide sequence, or the base represented by any of SEQ ID NOs 618 u has a nucleotide sequence, the complementary sequence that hybridizes to the nucleotide sequence is t in the sequence can be cited "nucleic acid". The "gene" does not ask another functional area, may include for example an expression control region, coding region, and exon or intron. Also, "gene" may be included in the cell, are released to the outside of cells may be present alone, it may be in a state of being encapsulated in the vesicles, called exosomes.
[0054]
The term "exosomes" as used herein, is a vesicle wrapped in a lipid bilayer membrane, which is secreted from the cell. Exosomes derived from multivesicular endosomes, may be when they are released into the extracellular environment, including RNA, biological materials, such as "gene" and protein such as DNA therein. Exosomes are known blood, serum, plasma, may be included in a body fluid such as lymph. Further, "exosomes" is sometimes commonly referred to as "exosomes".
[0055]
The term "transcription product" as used herein, refers to a DNA sequence of a gene of RNA synthesized as a template. Binds to a site where RNA polymerase is referred to as the promoter upstream of the gene, RNA is synthesized in a manner going as 3 'end is bound ribonucleotides be complementary to the base sequence of DNA. This RNA not only the gene itself, the expression control region, the coding region, contains the entire sequence from the transcription start site, including exons or introns up to the end of the poly (A) sequence.
[0056]
Further, "micro RNA (miRNAs)", as used herein, unless otherwise noted, are transcribed as an RNA precursor of the hairpin-like structure, is cleaved by the dsRNA cleavage enzyme having RNase III cleavage activity, a protein complex termed RISC incorporated into and used with the intention of non-coding RNA between 15 and 25 bases involved in mRNA translation inhibition. Also "miRNA" as used herein not only "miRNA" represented by a specific nucleotide sequence (or a SEQ ID NO), the precursor of the "miRNA" (pre-miRNA, pri-miRNA), and their a biological function equivalent miRNAs, for example homologues (i.e., homologs or orthologs), variants such as polymorphisms, and also encompasses derivatives. Such precursors, congeners, the variant or derivative, in particular, can be identified by miRBase release 20 (http://www.mirbase.org/), under stringent conditions as described later , can be cited "miRNA" having any complementary sequences which hybridize to the nucleotide sequence of the specific nucleotide sequence shown in any of SEQ ID NOs 618. Furthermore, "miRNA" as used herein may be a gene product of miR gene, such gene products are mature miRNA (e.g., involved in translational repression of the mRNA as described above 15 ~ 25 include a base, or 19 to 25 bases, non-coding RNA) or miRNA precursor (for example, the pre-miRNA or pri-miRNA, such as a).
[0057]
The term "probe" as used herein encompasses polynucleotides and / or complementary to the polynucleotide used for specifically detecting the resulting RNA or polynucleotides derived therefrom by expression of a gene.
[0058]
The term "primer" as used herein encompasses polynucleotides and / or complementary to the polynucleotide specifically recognizes the resulting RNA or polynucleotides derived therefrom by expression of the gene is amplified.
[0059]
Wherein complementary polynucleotide (complementary strand, reverse strand) to the base sequence u is t in the nucleotide sequence or the nucleotide sequence as defined by any of SEQ ID NOS: 1 to 618, from the consisting of polynucleotides full-length sequence, or a partial sequence, (for convenience here, this is referred to as positive strand) the a for: T (U), G: based on base pairing relationships such C, in a base complementary relationship It refers to a polynucleotide. However, such a complementary strand is not limited to the case of forming the base sequence and completely complementary sequence of the plus strand of interest, as it has a complementary relationship to the extent that can hybridize with the positive strand and the stringent conditions of interest there may be.
[0060]
The "stringent conditions" as used herein, to a greater extent than the nucleic acid probe to other sequences (e.g. background standard error × 2 or more measurements of the average + background measurement value of the measurement value), the It refers to hybridizing conditions to the target sequence. Stringent conditions are sequence-dependent and will be different depending on the environment the hybridization is performed. By controlling the stringency of the hybridization and / or washing conditions, target sequences can be identified is 100% complementary to the nucleic acid probe. Specific examples of the "stringent conditions" will be described later.
[0061]
The "Tm value" as used herein, the double-stranded portion of the polynucleotide is denatured into single-stranded, double-stranded and single-stranded 1: means the temperature which is present in a ratio.
[0062]
A "variant" as used herein, the case of nucleic acid, polymorphism variants of native caused such mutation, or any one of the nucleotide sequences of SEQ ID NOs 618 or the u in the nucleotide sequence nucleotide sequence which is t, or two or three or more base deletion in its partial sequence, substitution, variants, or of any of the sequences of SEQ ID NO: 1-618 precursor RNA containing the addition or insertion nucleotide sequence of (premature miRNA), or the nucleotide sequence u in the nucleotide sequence is t, or one or more base deletion in its partial sequence, substitution, addition or variant comprising an insertion, or the nucleotide sequence each or a partial sequence and about 90% or more of about 95% or more, about 97% or more, about 98% or more, poly including a mutant, or the nucleotide sequence or a partial sequence is shown about 99% or more of identity It means hybridizing nucleic acids under stringent conditions of nucleotide or oligonucleotide and the above definition.
[0063]
The term "several" as used herein, means about 10,9,8,7,6,5,4,3 or two integers.
[0064]
As used herein, mutants, site-directed mutagenesis, can be fabricated using well known techniques such as mutagenesis method using PCR method.
[0065]
"Identity", as used herein, using the search system of the protein or gene according to the above BLAST or FASTA, by introducing gaps, or not introducing gaps, can be determined (Zheng Zhang et al., 2000 . year, J.Comput.Biol, 7 Volume, p203-214;. Altschul, S.F et al., 1990, Journal of Molecular Biology, 215 volume, p403-410;. Pearson, W.R et al., 1988 , Proc.Natl.Acad.Sci.U.S.A., 85th Volume, p2444-2448).
[0066]
The term "derivative" as used herein, modified nucleic acids include, but are not limited to for example, labeled derivatives due fluorophore, modified nucleotides (e.g. halogen, alkyl such as methyl, alkoxy such as methoxy, thio, groups such as carboxymethyl reconstruction of nucleotides and bases including double bond saturation, deamination, derivatives including nucleotides, etc.) that has received and substitution of sulfur molecules of oxygen molecules, PNA (peptide nucleic acid; Nielsen, P.E. et al., 1991, Science, 254 vol, p1497-500), LNA (locked nucleic acid;. Obika, S et al., refers to 1998, Tetrahedron Lett, 39 vol, p5401-5404), and the like..
[0067]
"Nucleic acid" capable of binding to a polynucleotide specifically selected from miRNA is a lung marker described hereinabove is a nucleic acid that is synthesized or prepared, in particular, "nucleic acid probe" or "primer" hints, in order to detect the presence or absence of lung cancer in the subject, or the presence or absence of morbidity of lung cancer, the extent of the affected, the degree of presence and improvement of improvement of lung cancer, in order to diagnose a susceptibility to the treatment of lung cancer, or prevention of lung cancer, to screen for useful candidates for amelioration or treatment is directly or indirectly utilized. In vivo in relation to these in the diseased lung cancer, in particular blood, specifically recognize and bind the transcription product or cDNA thereof synthetic nucleic acid represented by any one of the sequences in the sample Nos. 1 to 618 body fluids such as urine nucleotides capable of, including oligonucleotides and polynucleotides. These nucleotides, oligonucleotides and polynucleotides, in a living body based on the nature, as a probe for detecting the gene expressed in such tissues or the cells and also for amplifying the gene expressed in vivo it can be effectively used as a primer.
[0068]
The term "detection" as used herein, testing, measurement, detection, or, may be replaced by the term decision support. Further, the term "evaluation" herein is used in its sense including at supporting diagnosis or evaluation based on the inspection results or measurement results.
[0069]
"Subject" as used herein includes humans, primates, including chimpanzees, dogs, pet animals such as cats, cows, horses, sheep, domestic animals such as goats, mice, rodents such as rats It means of a mammal. Further, "normal form" is also a such mammalian, means an animal not suffering from cancer to be detected.
[0070]
Probability is used "P" or "P-value" in the statistical test, the extreme statistic is observed than statistics calculated from actual data under the null hypothesis herein It is shown. Thus as the "P" or "P-value" is small, it considered that there are significant differences between the comparison.
[0071]
As used herein, "sensitivity" means the value of (number of true positives) / (Number of Number + false negative true positives). Sensitivity it is possible to discover a lung cancer at an early stage is higher, leading to a decrease in full cancers of resection and recurrence rate.
[0072]
As used herein, "specificity" refers to the (number of true negatives) / (Number of Number + false positive true negative). If the higher specificity of a healthy body to prevent the implementation of the useless additional testing due to misjudged and lung cancer patients, leading to a reduction of relief and medical expenses of the patient's burden.
[0073]
As used herein, "accuracy" means the value of (the number of number + True negatives of true positives) / (total number of cases). Accuracy shows the percentage determination result is correct with respect to all the samples, the first index to evaluate the detection performance.
[0074]
Judgment in the present specification, and becomes a "specimen" is the subject of detection or diagnosis, refers to the occurrence of lung cancer, the progression of lung cancer, and the organization and the biological material gene of the present invention is to expression changes with the exertion of therapeutic effect on lung cancer . Vascular lung tissue and around the in particular, organ lymph nodes and organs, also metastasis is suspected, skin, and blood, urine, saliva, sweat, body fluids such as tissue exudate, sera prepared from blood, plasma refers to other, feces, hair and the like. Furthermore the biological sample, specifically extracted from these refers to a gene, such as RNA or miRNA.
[0075]
The term as used herein, "hsa-miR-6768-5p gene" or "hsa-miR-6768-5p" is, hsa-miR-6768-5p gene (miRBase Accession described in SEQ ID NO: 1 No. MIMAT0027436) and other, including such species homologs or orthologs. hsa-miR-6768-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6768-5p" takes a hairpin-like structure "hsa-mir-6768" (miRBase Accession No.MI0022613, SEQ ID NO: 175) is known as its precursor.
[0076]
The term as used herein, "hsa-miR-6836-3p gene" or "hsa-miR-6836-3p" is, hsa-miR-6836-3p gene (miRBase Accession described in SEQ ID NO: 2 No. MIMAT0027575) and other, including such species homologs or orthologs. hsa-miR-6836-3p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6836-3p" takes a hairpin-like structure "hsa-mir-6836" (miRBase Accession No.MI0022682, SEQ ID NO: 176) is known as its precursor.
[0077]
The term as used herein, "hsa-miR-6782-5p gene" or "hsa-miR-6782-5p" is, hsa-miR-6782-5p gene (miRBase Accession described in SEQ ID NO: 3 No. MIMAT0027464) and other, including such species homologs or orthologs. hsa-miR-6782-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6782-5p" takes a hairpin-like structure "hsa-mir-6782" (miRBase Accession No.MI0022627, SEQ ID NO: 177) is known as its precursor.
[0078]
The term as used herein, "hsa-miR-3663-3p gene" or "hsa-miR-3663-3p" is, hsa-miR-3663-3p gene (miRBase Accession described in SEQ ID NO: 4 No. MIMAT0018085) and other, including such species homologs or orthologs. hsa-miR-3663-3p gene, it is possible to obtain Liao JY, et al., 2010, PLoS One, 5 Volume, by the method described in e10563. Further, "hsa-miR-3663-3p" takes a hairpin-like structure "hsa-mir-3663" (miRBase Accession No.MI0016064, SEQ ID NO: 178) is known as its precursor.
[0079]
The term as used herein, "hsa-miR-1908-3p gene" or "hsa-miR-1908-3p" is, hsa-miR-1908-3p gene (miRBase Accession described in SEQ ID NO: 5 of 5 No. MIMAT0026916) and other, including such species homologs or orthologs. hsa-miR-1908-3p gene, Bar M et al., 2008, Stem The Cells, 26 vol, may be obtained by the method described in p2496-2505. Further, "hsa-miR-1908-3p" takes a hairpin-like structure "hsa-mir-1908" (miRBase Accession No.MI0008329, SEQ ID NO: 179) is known as its precursor.
[0080]
The term as used herein, "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" is, hsa-miR-6726-5p gene (miRBase Accession described in SEQ ID NO. 6 No. MIMAT0027353) and other, including such species homologs or orthologs. hsa-miR-6726-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6726-5p" takes a hairpin-like structure "hsa-mir-6726" (miRBase Accession No.MI0022571, SEQ ID NO: 180) is known as its precursor.
[0081]
The term as used herein, "hsa-miR-4258 gene" or "hsa-miR-4258" is, hsa-miR-4258 gene described in SEQ ID NO: 7 (miRBase Accession No.MIMAT0016879) and other species It encompasses such homologs or orthologs. hsa-miR-4258 gene can be obtained Goff LA et al., 2009, PLoS One, 4 vol., by the method described in e7192. Further, "hsa-miR-4258" takes a hairpin-like structure "hsa-mir-4258" (miRBase Accession No.MI0015857, SEQ ID NO: 181) is known as its precursor.
[0082]
The term as used herein, "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" is, hsa-miR-1343-3p gene (miRBase Accession described in SEQ ID NO. 8 No. MIMAT0019776) and other, including such species homologs or orthologs. hsa-miR-1343-3p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-1343-3p" takes a hairpin-like structure "hsa-mir-1343" (miRBase Accession No.MI0017320, SEQ ID NO: 182) is known as its precursor.
[0083]
The term as used herein, "hsa-miR-4516 gene" or "hsa-miR-4516" is, hsa-miR-4516 gene described in SEQ ID NO: 9 (miRBase Accession No.MIMAT0019053) and other species It encompasses such homologs or orthologs. hsa-miR-4516 gene, Jima DD et al., 2010, Blood, 116 vol, may be obtained by the method described in e118-e127. Further, "hsa-miR-4516" takes a hairpin-like structure "hsa-mir-4516" (miRBase Accession No.MI0016882, SEQ ID NO: 183) is known as its precursor.
[0084]
The term as used herein, "hsa-miR-6875-5p gene" or "hsa-miR-6875-5p" is, hsa-miR-6875-5p gene (miRBase Accession described in SEQ ID NO: 10 No. MIMAT0027650) and other, including such species homologs or orthologs. hsa-miR-6875-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6875-5p" takes a hairpin-like structure "hsa-mir-6875" (miRBase Accession No.MI0022722, SEQ ID NO: 184) is known as its precursor.
[0085]
The term as used herein, "hsa-miR-4651 gene" or "hsa-miR-4651" is, hsa-miR-4651 gene described in SEQ ID NO: 11 (miRBase Accession No.MIMAT0019715) and other species It encompasses such homologs or orthologs. hsa-miR-4651 gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4651" takes a hairpin-like structure "hsa-mir-4651" (miRBase Accession No.MI0017279, SEQ ID NO: 185) is known as its precursor.
[0086]
The term as used herein, "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" is, hsa-miR-6825-5p gene (miRBase Accession described in SEQ ID NO. 12 No. MIMAT0027550) and other, including such species homologs or orthologs. hsa-miR-6825-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6825-5p" takes a hairpin-like structure "hsa-mir-6825" (miRBase Accession No.MI0022670, SEQ ID NO: 186) is known as its precursor.
[0087]
The term as used herein, "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" is, hsa-miR-6840-3p gene (miRBase Accession described in SEQ ID NO. 13 No. MIMAT0027583) and other, including such species homologs or orthologs. hsa-miR-6840-3p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6840-3p" takes a hairpin-like structure "hsa-mir-6840" (miRBase Accession No.MI0022686, SEQ ID NO: 187) is known as its precursor.
[0088]
The term as used herein, "hsa-miR-6780b-5p gene" or "hsa-miR-6780b-5p" is, hsa-miR-6780b-5p gene described in SEQ ID NO: 14 (miRBase Accession No. MIMAT0027572) and other, including such species homologs or orthologs. hsa-miR-6780b-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6780b-5p" takes a hairpin-like structure "hsa-mir-6780b" (miRBase Accession No.MI0022681, SEQ ID NO: 188) is known as its precursor.
[0089]
The term as used herein, "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" is, hsa-miR-6749-5p gene (miRBase Accession described in SEQ ID NO: 15 No. MIMAT0027398) and other, including such species homologs or orthologs. hsa-miR-6749-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6749-5p" takes a hairpin-like structure "hsa-mir-6749" (miRBase Accession No.MI0022594, SEQ ID NO: 189) is known as its precursor.
[0090]
The term as used herein, "hsa-miR-8063 gene" or "hsa-miR-8063" is, hsa-miR-8063 gene described in SEQ ID NO: 16 (miRBase Accession No.MIMAT0030990) and other species It encompasses such homologs or orthologs. hsa-miR-8063 gene, Wang HJ, et al., 2013, Shock, 39 vol, may be obtained by the method described in p480-487. Further, "hsa-miR-8063" takes a hairpin-like structure "hsa-mir-8063" (miRBase Accession No.MI0025899, SEQ ID NO: 190) is known as its precursor.
[0091]
The term as used herein, "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" is, hsa-miR-6784-5p gene (miRBase Accession described in SEQ ID NO. 17 No. MIMAT0027468) and other, including such species homologs or orthologs. hsa-miR-6784-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6784-5p" takes a hairpin-like structure "hsa-mir-6784" (miRBase Accession No.MI0022629, SEQ ID NO: 191) is known as its precursor.
[0092]
The term as used herein, "hsa-miR-3679-5p gene" or "hsa-miR-3679-5p" is, hsa-miR-3679-5p gene (miRBase Accession set forth in SEQ ID NO: 18 No. MIMAT0018104) and other, including such species homologs or orthologs. hsa-miR-3679-5p gene, it is possible to obtain Creighton CJ, et al., 2010, PLoS One, 5 Volume, by the method described in the e9637. Further, "hsa-miR-3679-5p" takes a hairpin-like structure "hsa-mir-3679" (miRBase Accession No.MI0016080, SEQ ID NO: 192) is known as its precursor.
[0093]
The term as used herein, "hsa-miR-3184-5p gene" or "hsa-miR-3184-5p" is, hsa-miR-3184-5p gene (miRBase Accession set forth in SEQ ID NO. 19 No. MIMAT0015064) and other, including such species homologs or orthologs. hsa-miR-3184-5p gene, Stark MS, et al., 2010, PLoS One, 5 volumes, can be obtained by the methods described in the e9685. Further, "hsa-miR-3184-5p" takes a hairpin-like structure "hsa-mir-3184" (miRBase Accession No.MI0014226, SEQ ID NO: 193) is known as its precursor.
[0094]
The term as used herein, "hsa-miR-663b gene" or "hsa-miR-663b" are, hsa-miR-663b gene described in SEQ ID NO: 20 (miRBase Accession No.MIMAT0005867) and other species It encompasses such homologs or orthologs. hsa-miR-663b gene, Takada S, et al., 2008, Leukemia, 22 vol., can be obtained by the method described in p1274-1278. Further, "hsa-miR-663b 'assumes a hairpin-like structure" hsa-mir-663b "(miRBase Accession No.MI0006336, SEQ ID NO: 194) is known as its precursor.
[0095]
The term as used herein, "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" is, hsa-miR-6880-5p gene (miRBase Accession described in SEQ ID NO: 21 No. MIMAT0027660) and other, including such species homologs or orthologs. hsa-miR-6880-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6880-5p" takes a hairpin-like structure "hsa-mir-6880" (miRBase Accession No.MI0022727, SEQ ID NO: 195) is known as its precursor.
[0096]
The term as used herein, "hsa-miR-1908-5p gene" or "hsa-miR-1908-5p" is, hsa-miR-1908-5p gene (miRBase Accession described in SEQ ID NO: 22 No. MIMAT0007881) and other, including such species homologs or orthologs. hsa-miR-1908-5p gene, Bar M et al., 2008, Stem The Cells, 26 vol, may be obtained by the method described in p2496-2505. Further, "hsa-miR-1908-5p" takes a hairpin-like structure "hsa-mir-1908" (miRBase Accession No.MI0008329, SEQ ID NO: 179) is known as its precursor.
[0097]
The term as used herein, "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" is set forth in SEQ ID NO: 23 hsa-miR-92a-2-5p It encompasses such as a gene (miRBase Accession No.MIMAT0004508) and other species homologs or orthologs. hsa-miR-92a-2-5p gene can be obtained Mourelatos Z-al, 2002, Genes Dev, 16 vol., by the method described in p720-728. Further, "hsa-miR-92a-2-5p" takes a hairpin-like structure "hsa-mir-92a-2" (miRBase Accession No.MI0000094, SEQ ID NO: 196) is known as its precursor.
[0098]
The term as used herein, "hsa-miR-7975 gene" or "hsa-miR-7975" is, hsa-miR-7975 gene described in SEQ ID NO: 24 (miRBase Accession No.MIMAT0031178) and other species It encompasses such homologs or orthologs. hsa-miR-7975 gene, Velthut-Meikas A, et al., 2013, may be obtained by the methods described Mol Endocrinol, online version, to. Further, "hsa-miR-7975" takes a hairpin-like structure "hsa-mir-7975" (miRBase Accession No.MI0025751, SEQ ID NO: 197) is known as its precursor.
[0099]
The term as used herein, "hsa-miR-7110-5p gene" or "hsa-miR-7110-5p" is, hsa-miR-7110-5p gene (miRBase Accession described in SEQ ID NO: 25 No. MIMAT0028117) and other, including such species homologs or orthologs. hsa-miR-7110-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-7110-5p" takes a hairpin-like structure "hsa-mir-7110" (miRBase Accession No.MI0022961, SEQ ID NO: 198) is known as its precursor.
[0100]
The term as used herein, "hsa-miR-6842-5p gene" or "hsa-miR-6842-5p" is, hsa-miR-6842-5p gene (miRBase Accession described in SEQ ID NO: 26 No. MIMAT0027586) and other, including such species homologs or orthologs. hsa-miR-6842-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6842-5p" takes a hairpin-like structure "hsa-mir-6842" (miRBase Accession No.MI0022688, SEQ ID NO: 199) is known as its precursor.
[0101]
The term as used herein, "hsa-miR-6857-5p gene" or "hsa-miR-6857-5p" is, hsa-miR-6857-5p gene (miRBase Accession described in SEQ ID NO: 27 No. MIMAT0027614) and other, including such species homologs or orthologs. hsa-miR-6857-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6857-5p" takes a hairpin-like structure "hsa-mir-6857" (miRBase Accession No.MI0022703, SEQ ID NO: 200) is known as its precursor.
[0102]
The term as used herein, "hsa-miR-5572 gene" or "hsa-miR-5572" is, hsa-miR-5572 gene described in SEQ ID NO: 28 (miRBase Accession No.MIMAT0022260) and other species It encompasses such homologs or orthologs. hsa-miR-5572 gene can be obtained Tandon M et al., 2012, Oral Dis, 18 vol., by the method described in p127-131. Further, "hsa-miR-5572" takes a hairpin-like structure "hsa-mir-5572" (miRBase Accession No.MI0019117, SEQ ID NO: 201) is known as its precursor.
[0103]
The term as used herein, "hsa-miR-3197 gene" or "hsa-miR-3197" is, hsa-miR-3197 gene described in SEQ ID NO: 29 (miRBase Accession No.MIMAT0015082) and other species It encompasses such homologs or orthologs. hsa-miR-3197 gene, Stark MS, et al., 2010, PLoS One, 5 volumes, can be obtained by the methods described in the e9685. Further, "hsa-miR-3197" takes a hairpin-like structure "hsa-mir-3197" (miRBase Accession No.MI0014245, SEQ ID NO: 202) is known as its precursor.
[0104]
The term as used herein, "hsa-miR-6131 gene" or "hsa-miR-6131" is, hsa-miR-6131 gene described in SEQ ID NO: 30 (miRBase Accession No.MIMAT0024615) and other species It encompasses such homologs or orthologs. hsa-miR-6131 gene, Dannemann M, et al., 2012, Genome Biol Evol, 4 volumes, can be obtained by the methods described in p552-564. Further, "hsa-miR-6131" takes a hairpin-like structure "hsa-mir-6131" (miRBase Accession No.MI0021276, SEQ ID NO: 203) is known as its precursor.
[0105]
The term as used herein, "hsa-miR-6889-5p gene" or "hsa-miR-6889-5p" is, hsa-miR-6889-5p gene (miRBase Accession described in SEQ ID NO: 31 No. MIMAT0027678) and other, including such species homologs or orthologs. hsa-miR-6889-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6889-5p" takes a hairpin-like structure "hsa-mir-6889" (miRBase Accession No.MI0022736, SEQ ID NO: 204) is known as its precursor.
[0106]
The term as used herein, "hsa-miR-4454 gene" or "hsa-miR-4454" is, hsa-miR-4454 gene described in SEQ ID NO: 32 (miRBase Accession No.MIMAT0018976) and other species It encompasses such homologs or orthologs. hsa-miR-4454 gene, Jima DD, et al., 2010, Blood, 116 volumes, can be obtained by the methods described in the e118-e127. Further, "hsa-miR-4454" takes a hairpin-like structure "hsa-mir-4454" (miRBase Accession No.MI0016800, SEQ ID NO: 205) is known as its precursor.
[0107]
The term as used herein, "hsa-miR-1199-5p gene" or "hsa-miR-1199-5p" is, hsa-miR-1199-5p gene (miRBase Accession described in SEQ ID NO: 33 No. MIMAT0031119) and other, including such species homologs or orthologs. hsa-miR-1199-5p gene, Salvi A, et al., 2013, Int J Oncol, 42 volumes, can be obtained by the methods described in the p391-402. Further, "hsa-miR-1199-5p" takes a hairpin-like structure "hsa-mir-1199" (miRBase Accession No.MI0020340, SEQ ID NO: 206) is known as its precursor.
[0108]
The term as used herein, "hsa-miR-1247-3p gene" or "hsa-miR-1247-3p" is, hsa-miR-1247-3p gene (miRBase Accession described in SEQ ID NO: 34 No. MIMAT0022721) and other, including such species homologs or orthologs. hsa-miR-1247-3p gene, Morin RD et al., 2008, Genome Res, 18 vol., can be obtained by the method described in p610-621. Further, "hsa-miR-1247-3p" takes a hairpin-like structure "hsa-mir-1247" (miRBase Accession No.MI0006382, SEQ ID NO: 207) is known as its precursor.
[0109]
The term as used herein, "hsa-miR-6800-5p gene" or "hsa-miR-6800-5p" is, hsa-miR-6800-5p gene (miRBase Accession described in SEQ ID NO: 35 No. MIMAT0027500) and other, including such species homologs or orthologs. hsa-miR-6800-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6800-5p" takes a hairpin-like structure "hsa-mir-6800" (miRBase Accession No.MI0022645, SEQ ID NO: 208) is known as its precursor.
[0110]
The term as used herein, "hsa-miR-6872-3p gene" or "hsa-miR-6872-3p" is, hsa-miR-6872-3p gene (miRBase Accession described in SEQ ID NO: 36 No. MIMAT0027645) and other, including such species homologs or orthologs. hsa-miR-6872-3p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6872-3p" takes a hairpin-like structure "hsa-mir-6872" (miRBase Accession No.MI0022719, SEQ ID NO: 209) is known as its precursor.
[0111]
The term as used herein, "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" is, hsa-miR-4649-5p gene (miRBase Accession described in SEQ ID NO: 37 No. MIMAT0019711) and other, including such species homologs or orthologs. hsa-miR-4649-5p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4649-5p" takes a hairpin-like structure "hsa-mir-4649" (miRBase Accession No.MI0017276, SEQ ID NO: 210) is known as its precursor.
[0112]
The term as used herein, "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" is, hsa-miR-6791-5p gene (miRBase Accession set forth in SEQ ID NO: 38 No. MIMAT0027482) and other, including such species homologs or orthologs. hsa-miR-6791-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6791-5p" takes a hairpin-like structure "hsa-mir-6791" (miRBase Accession No.MI0022636, SEQ ID NO: 211) is known as its precursor.
[0113]
The term as used herein, "hsa-miR-4433b-3p gene" or "hsa-miR-4433b-3p" is, hsa-miR-4433b-3p gene described in SEQ ID NO: 39 (miRBase Accession No. MIMAT0030414) and other, including such species homologs or orthologs. hsa-miR-4433b-3p genes, it is possible to obtain Ple H, et al., 2012, PLoS One, 7 vol., by the method described in e50746. Further, "hsa-miR-4433b-3p" takes a hairpin-like structure "hsa-mir-4433b" (miRBase Accession No.MI0025511, SEQ ID NO: 212) is known as its precursor.
[0114]
The term as used herein, "hsa-miR-3135b gene" or "hsa-miR-3135b" is, hsa-miR-3135b gene described in SEQ ID NO: 40 (miRBase Accession No.MIMAT0018985) and other species It encompasses such homologs or orthologs. hsa-miR-3135b gene, Jima DD, et al., 2010, Blood, 116 volumes, can be obtained by the methods described in the e118-e127. Further, "hsa-miR-3135b" takes a hairpin-like structure "hsa-mir-3135b" (miRBase Accession No.MI0016809, SEQ ID NO: 213) is known as its precursor.
[0115]
The term as used herein, "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" is set forth in SEQ ID NO: 41 hsa-miR-128-2-5p It encompasses such as a gene (miRBase Accession No.MIMAT0031095) and other species homologs or orthologs. hsa-miR-128-2-5p gene, Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, can be obtained by the method described in p735-739. Further, "hsa-miR-128-2-5p" takes a hairpin-like structure "hsa-mir-128-2" (miRBase Accession No.MI0000727, SEQ ID NO: 214) is known as its precursor.
[0116]
The term as used herein, "hsa-miR-4675 gene" or "hsa-miR-4675" is, hsa-miR-4675 gene described in SEQ ID NO: 42 (miRBase Accession No.MIMAT0019757) and other species It encompasses such homologs or orthologs. hsa-miR-4675 gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4675" takes a hairpin-like structure "hsa-mir-4675" (miRBase Accession No.MI0017306, SEQ ID NO: 215) is known as its precursor.
[0117]
The term as used herein, "hsa-miR-4472 gene" or "hsa-miR-4472" is, hsa-miR-4472 gene described in SEQ ID NO: 43 (miRBase Accession No.MIMAT0018999) and other species It encompasses such homologs or orthologs. hsa-miR-4472 gene, Jima DD, et al., 2010, Blood, 116 volumes, can be obtained by the methods described in the e118-e127. In addition, "hsa-miR-4472" takes a hairpin-like structure as its precursor "hsa-mir-4472-1, hsa-mir-4472-2" (miRBase Accession No.MI0016823, MI0016824, SEQ ID NO: 216, 217) is known.
[0118]
The term as used herein, "hsa-miR-6785-5p gene" or "hsa-miR-6785-5p" is, hsa-miR-6785-5p gene (miRBase Accession described in SEQ ID NO: 44 No. MIMAT0027470) and other, including such species homologs or orthologs. hsa-miR-6785-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6785-5p" takes a hairpin-like structure "hsa-mir-6785" (miRBase Accession No.MI0022630, SEQ ID NO: 218) is known as its precursor.
[0119]
The term as used herein, "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" is, hsa-miR-6741-5p gene (miRBase Accession set forth in SEQ ID NO: 45 No. MIMAT0027383) and other, including such species homologs or orthologs. hsa-miR-6741-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6741-5p" takes a hairpin-like structure "hsa-mir-6741" (miRBase Accession No.MI0022586, SEQ ID NO: 219) is known as its precursor.
[0120]
The term as used herein, "hsa-miR-7977 gene" or "hsa-miR-7977" is, hsa-miR-7977 gene described in SEQ ID NO: 46 (miRBase Accession No.MIMAT0031180) and other species It encompasses such homologs or orthologs. hsa-miR-7977 gene, Velthut-Meikas A, et al., 2013, may be obtained by the methods described Mol Endocrinol, online version, to. Further, "hsa-miR-7977" takes a hairpin-like structure "hsa-mir-7977" (miRBase Accession No.MI0025753, SEQ ID NO: 220) is known as its precursor.
[0121]
The term as used herein, "hsa-miR-3665 gene" or "hsa-miR-3665" is, hsa-miR-3665 gene described in SEQ ID NO: 47 (miRBase Accession No.MIMAT0018087) and other species It encompasses such homologs or orthologs. hsa-miR-3665 gene, Xie X-et al., 2005, Nature, 434 vol, may be obtained by the method described in p338-345. Further, "hsa-miR-3665" takes a hairpin-like structure "hsa-mir-3665" (miRBase Accession No.MI0016066, SEQ ID NO: 221) is known as its precursor.
[0122]
The term as used herein, "hsa-miR-128-1-5p gene" or "hsa-miR-128-1-5p" is set forth in SEQ ID NO: 48 hsa-miR-128-1-5p It encompasses such as a gene (miRBase Accession No.MIMAT0026477) and other species homologs or orthologs. hsa-miR-128-1-5p gene, Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, can be obtained by the method described in p735-739. Further, "hsa-miR-128-1-5p" takes a hairpin-like structure "hsa-mir-128-1" (miRBase Accession No.MI0000447, SEQ ID NO: 222) is known as its precursor.
[0123]
The term as used herein, "hsa-miR-4286 gene" or "hsa-miR-4286" is, hsa-miR-4286 gene described in SEQ ID NO: 49 (miRBase Accession No.MIMAT0016916) and other species It encompasses such homologs or orthologs. hsa-miR-4286 gene can be obtained Goff LA et al., 2009, PLoS One, 4 vol., by the method described in e7192. Further, "hsa-miR-4286" takes a hairpin-like structure "hsa-mir-4286" (miRBase Accession No.MI0015894, SEQ ID NO: 223) is known as its precursor.
[0124]
The term as used herein, "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" is, hsa-miR-6765-3p gene (miRBase Accession set forth in SEQ ID NO: 50 No. MIMAT0027431) and other, including such species homologs or orthologs. hsa-miR-6765-3p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6765-3p" takes a hairpin-like structure "hsa-mir-6765" (miRBase Accession No.MI0022610, SEQ ID NO: 224) is known as its precursor.
[0125]
The term as used herein, "hsa-miR-4632-5p gene" or "hsa-miR-4632-5p" is, hsa-miR-4632-5p gene (miRBase Accession described in SEQ ID NO: 51 No. MIMAT0022977) and other, including such species homologs or orthologs. hsa-miR-4632-5p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4632-5p" takes a hairpin-like structure "hsa-mir-4632" (miRBase Accession No.MI0017259, SEQ ID NO: 225) is known as its precursor.
[0126]
The term as used herein, "hsa-miR-365a-5p gene" or "hsa-miR-365a-5p" is, hsa-miR-365a-5p gene described in SEQ ID NO: 52 (miRBase Accession No. MIMAT0009199) and other, including such species homologs or orthologs. hsa-miR-365a-5p gene, Xie X-et al., 2005, Nature, 434 vol, may be obtained by the method described in p338-345. Further, "hsa-miR-365a-5p" takes a hairpin-like structure "hsa-mir-365a" (miRBase Accession No.MI0000767, SEQ ID NO: 226) is known as its precursor.
[0127]
The term as used herein, "hsa-miR-6088 gene" or "hsa-miR-6088" is, hsa-miR-6088 gene described in SEQ ID NO: 53 (miRBase Accession No.MIMAT0023713) and other species It encompasses such homologs or orthologs. hsa-miR-6088 gene can be obtained Yoo JK et al., 2012, Stem Cells Dev, 21 vol., by the method described in p2049-2057. Further, "hsa-miR-6088" takes a hairpin-like structure "hsa-mir-6088" (miRBase Accession No.MI0020365, SEQ ID NO: 227) is known as its precursor.
[0128]
The term as used herein, "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" is, hsa-miR-6816-5p gene (miRBase Accession described in SEQ ID NO: 54 No. MIMAT0027532) and other, including such species homologs or orthologs. hsa-miR-6816-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6816-5p" takes a hairpin-like structure "hsa-mir-6816" (miRBase Accession No.MI0022661, SEQ ID NO: 228) is known as its precursor.
[0129]
The term as used herein, "hsa-miR-6885-5p gene" or "hsa-miR-6885-5p" is, hsa-miR-6885-5p gene (miRBase Accession described in SEQ ID NO: 55 No. MIMAT0027670) and other, including such species homologs or orthologs. hsa-miR-6885-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6885-5p" takes a hairpin-like structure "hsa-mir-6885" (miRBase Accession No.MI0022732, SEQ ID NO: 229) is known as its precursor.
[0130]
The term as used herein, "hsa-miR-711 gene" or "hsa-miR-711" is, hsa-miR-711 gene described in SEQ ID NO: 56 (miRBase Accession No.MIMAT0012734) and other species It encompasses such homologs or orthologs. hsa-miR-711 gene, Artzi S et al., 2008, BMC Bioinformatics,. 9 vol, may be obtained by the method described in p39. Further, "hsa-miR-711" takes a hairpin-like structure "hsa-mir-711" (miRBase Accession No.MI0012488, SEQ ID NO: 230) is known as its precursor.
[0131]
The term as used herein, "hsa-miR-6765-5p gene" or "hsa-miR-6765-5p" is, hsa-miR-6765-5p gene (miRBase Accession described in SEQ ID NO: 57 No. MIMAT0027430) and other, including such species homologs or orthologs. hsa-miR-6765-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6765-5p" takes a hairpin-like structure "hsa-mir-6765" (miRBase Accession No.MI0022610, SEQ ID NO: 224) is known as its precursor.
[0132]
The term as used herein, "hsa-miR-3180 gene" or "hsa-miR-3180" is, hsa-miR-3180 gene described in SEQ ID NO: 58 (miRBase Accession No.MIMAT0018178) and other species It encompasses such homologs or orthologs. hsa-miR-3180 gene can be obtained Creighton CJ et al., 2010, PLoS One, 5 of 5 vol., by the method described in e9637. In addition, "hsa-miR-3180" takes a hairpin-like structure as its precursor "hsa-mir-3180-4, hsa-mir-3180-5" (miRBase Accession No.MI0016408, MI0016409, SEQ ID NO: 231, 232) is known.
[0133]
The term as used herein, "hsa-miR-4442 gene" or "hsa-miR-4442" is, hsa-miR-4442 gene described in SEQ ID NO: 59 (miRBase Accession No.MIMAT0018960) and other species It encompasses such homologs or orthologs. hsa-miR-4442 gene, Jima DD et al., 2010, Blood, 116 vol, may be obtained by the method described in e118-e127. Further, "hsa-miR-4442" takes a hairpin-like structure "hsa-mir-4442" (miRBase Accession No.MI0016785, SEQ ID NO: 233) is known as its precursor.
[0134]
The term as used herein, "hsa-miR-4792 gene" or "hsa-miR-4792" is, hsa-miR-4792 gene described in SEQ ID NO: 60 (miRBase Accession No.MIMAT0019964) and other species It encompasses such homologs or orthologs. hsa-miR-4792 gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4792" takes a hairpin-like structure "hsa-mir-4792" (miRBase Accession No.MI0017439, SEQ ID NO: 234) is known as its precursor.
[0135]
The term as used herein, "hsa-miR-6721-5p gene" or "hsa-miR-6721-5p" is, hsa-miR-6721-5p gene (miRBase Accession described in SEQ ID NO: 61 No. MIMAT0025852) and other, including such species homologs or orthologs. hsa-miR-6721-5p gene, Li Y-et al., 2012, Gene, 497 vol, may be obtained by the method described in p330-335. Further, "hsa-miR-6721-5p" takes a hairpin-like structure "hsa-mir-6721" (miRBase Accession No.MI0022556, SEQ ID NO: 235) is known as its precursor.
[0136]
The term as used herein, "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" is, hsa-miR-6798-5p gene (miRBase Accession described in SEQ ID NO: 62 No. MIMAT0027496) and other, including such species homologs or orthologs. hsa-miR-6798-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6798-5p" takes a hairpin-like structure "hsa-mir-6798" (miRBase Accession No.MI0022643, SEQ ID NO: 236) is known as its precursor.
[0137]
The term as used herein, "hsa-miR-3162-5p gene" or "hsa-miR-3162-5p" is, hsa-miR-3162-5p gene (miRBase Accession described in SEQ ID NO: 63 No. MIMAT0015036) and other, including such species homologs or orthologs. hsa-miR-3162-5p gene, Stark MS, et al., 2010, PLoS One, 5 volumes, can be obtained by the methods described in the e9685. Further, "hsa-miR-3162-5p" takes a hairpin-like structure "hsa-mir-3162" (miRBase Accession No.MI0014192, SEQ ID NO: 237) is known as its precursor.
[0138]
The term as used herein, "hsa-miR-6126 gene" or "hsa-miR-6126" is, hsa-miR-6126 gene described in SEQ ID NO: 64 (miRBase Accession No.MIMAT0024599) and other species It encompasses such homologs or orthologs. hsa-miR-6126 gene, Smith JL et al., 2012, J Virol, 86 vol., can be obtained by the method described in p5278-5287. Further, "hsa-miR-6126" takes a hairpin-like structure "hsa-mir-6126" (miRBase Accession No.MI0021260, SEQ ID NO: 238) is known as its precursor.
[0139]
The term as used herein, "hsa-miR-4758-5p gene" or "hsa-miR-4758-5p" is, hsa-miR-4758-5p gene (miRBase Accession described in SEQ ID NO: 65 No. MIMAT0019903) and other, including such species homologs or orthologs. hsa-miR-4758-5p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4758-5p" takes a hairpin-like structure "hsa-mir-4758" (miRBase Accession No.MI0017399, SEQ ID NO: 239) is known as its precursor.
[0140]
The term as used herein, "hsa-miR-2392 gene" or "hsa-miR-2392" is, hsa-miR-2392 gene described in SEQ ID NO: 66 (miRBase Accession No.MIMAT0019043) and other species It encompasses such homologs or orthologs. hsa-miR-2392 gene, Jima DD et al., 2010, Blood, 116 vol, may be obtained by the method described in e118-e127. Further, "hsa-miR-2392" takes a hairpin-like structure "hsa-mir-2392" (miRBase Accession No.MI0016870, SEQ ID NO: 240) is known as its precursor.
[0141]
The term as used herein, "hsa-miR-486-3p gene" or "hsa-miR-486-3p" is, hsa-miR-486-3p gene (miRBase Accession described in SEQ ID NO: 67 No. MIMAT0004762) and other, including such species homologs or orthologs. hsa-miR-486-3p gene, Fu H et al., 2005, FEBS Lett, 579 vol, may be obtained by the method described in p3849-3854. In addition, "hsa-miR-486-3p" takes a hairpin-like structure as its precursor "hsa-mir-486, hsa-mir-486-2" (miRBase Accession No.MI0002470, MI0023622, SEQ ID NO: 241, 242) is known.
[0142]
The term as used herein, "hsa-miR-6727-5p gene" or "hsa-miR-6727-5p" is, hsa-miR-6727-5p gene (miRBase Accession described in SEQ ID NO: 68 No. MIMAT0027355) and other, including such species homologs or orthologs. hsa-miR-6727-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6727-5p" takes a hairpin-like structure "hsa-mir-6727" (miRBase Accession No.MI0022572, SEQ ID NO: 243) is known as its precursor.
[0143]
The term as used herein, "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" is, hsa-miR-4728-5p gene (miRBase Accession described in SEQ ID NO: 69 No. MIMAT0019849) and other, including such species homologs or orthologs. hsa-miR-4728-5p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4728-5p" takes a hairpin-like structure "hsa-mir-4728" (miRBase Accession No.MI0017365, SEQ ID NO: 244) is known as its precursor.
[0144]
The term as used herein, "hsa-miR-6746-5p gene" or "hsa-miR-6746-5p" is, hsa-miR-6746-5p gene (miRBase Accession described in SEQ ID NO: 70 No. MIMAT0027392) and other, including such species homologs or orthologs. hsa-miR-6746-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6746-5p" takes a hairpin-like structure "hsa-mir-6746" (miRBase Accession No.MI0022591, SEQ ID NO: 245) is known as its precursor.
[0145]
The term as used herein, "hsa-miR-4270 gene" or "hsa-miR-4270" is, hsa-miR-4270 gene described in SEQ ID NO: 71 (miRBase Accession No.MIMAT0016900) and other species It encompasses such homologs or orthologs. hsa-miR-4270 gene can be obtained Goff LA et al., 2009, PLoS One, 4 vol., by the method described in e7192. Further, "hsa-miR-4270" takes a hairpin-like structure "hsa-mir-4270" (miRBase Accession No.MI0015878, SEQ ID NO: 246) is known as its precursor.
[0146]
The term as used herein, "hsa-miR-3940-5p gene" or "hsa-miR-3940-5p" is, hsa-miR-3940-5p gene (miRBase Accession described in SEQ ID NO: 72 No. MIMAT0019229) and other, including such species homologs or orthologs. hsa-miR-3940-5p gene, it is possible to obtain Liao JY, et al., 2010, PLoS One, 5 Volume, by the method described in e10563. Further, "hsa-miR-3940-5p" takes a hairpin-like structure "hsa-mir-3940" (miRBase Accession No.MI0016597, SEQ ID NO: 247) is known as its precursor.
[0147]
The term as used herein, "hsa-miR-4725-3p gene" or "hsa-miR-4725-3p" is, hsa-miR-4725-3p gene (miRBase Accession described in SEQ ID NO: 73 No. MIMAT0019844) and other, including such species homologs or orthologs. hsa-miR-4725-3p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4725-3p" takes a hairpin-like structure "hsa-mir-4725" (miRBase Accession No.MI0017362, SEQ ID NO: 248) is known as its precursor.
[0148]
The term as used herein, "hsa-miR-7108-5p gene" or "hsa-miR-7108-5p" is, hsa-miR-7108-5p gene (miRBase Accession described in SEQ ID NO: 74 No. MIMAT0028113) and other, including such species homologs or orthologs. hsa-miR-7108-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-7108-5p" takes a hairpin-like structure "hsa-mir-7108" (miRBase Accession No.MI0022959, SEQ ID NO: 249) is known as its precursor.
[0149]
The term as used herein, "hsa-miR-3656 gene" or "hsa-miR-3656" is, hsa-miR-3656 gene described in SEQ ID NO: 75 (miRBase Accession No.MIMAT0018076) and other species It encompasses such homologs or orthologs. hsa-miR-3656 gene, Meiri E et al., 2010, Nucleic Acids Res, 38 vol., can be obtained by the method described in p6234-6246. Further, "hsa-miR-3656" takes a hairpin-like structure "hsa-mir-3656" (miRBase Accession No.MI0016056, SEQ ID NO: 250) is known as its precursor.
[0150]
The term as used herein, "hsa-miR-6879-5p gene" or "hsa-miR-6879-5p" is, hsa-miR-6879-5p gene (miRBase Accession described in SEQ ID NO: 76 No. MIMAT0027658) and other, including such species homologs or orthologs. hsa-miR-6879-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6879-5p" takes a hairpin-like structure "hsa-mir-6879" (miRBase Accession No.MI0022726, SEQ ID NO: 251) is known as its precursor.
[0151]
The term as used herein, "hsa-miR-6738-5p gene" or "hsa-miR-6738-5p" is, hsa-miR-6738-5p gene (miRBase Accession described in SEQ ID NO: 77 No. MIMAT0027377) and other, including such species homologs or orthologs. hsa-miR-6738-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6738-5p" takes a hairpin-like structure "hsa-mir-6738" (miRBase Accession No.MI0022583, SEQ ID NO: 252) is known as its precursor.
[0152]
The term as used herein, "hsa-miR-1260a gene" or "hsa-miR-1260a" is, hsa-miR-1260a gene described in SEQ ID NO: 78 (miRBase Accession No.MIMAT0005911) and other species It encompasses such homologs or orthologs. hsa-miR-1260a gene, Morin RD et al., 2008, Genome Res, 18 vol., can be obtained by the method described in p610-621. Further, "hsa-miR-1260a" takes a hairpin-like structure "hsa-mir-1260a" (miRBase Accession No.MI0006394, SEQ ID NO: 253) is known as its precursor.
[0153]
The term as used herein, "hsa-miR-4446-3p gene" or "hsa-miR-4446-3p" is, hsa-miR-4446-3p gene (miRBase Accession described in SEQ ID NO: 79 No. MIMAT0018965) and other, including such species homologs or orthologs. hsa-miR-4446-3p gene, Jima DD, et al., 2010, Blood, 116 volumes, can be obtained by the methods described in the e118-e127. Further, "hsa-miR-4446-3p" takes a hairpin-like structure "hsa-mir-4446" (miRBase Accession No.MI0016789, SEQ ID NO: 254) is known as its precursor.
[0154]
The term as used herein, "hsa-miR-3131 gene" or "hsa-miR-3131" is, hsa-miR-3131 gene described in SEQ ID NO: 80 (miRBase Accession No.MIMAT0014996) and other species It encompasses such homologs or orthologs. hsa-miR-3131 gene, Stark MS, et al., 2010, PLoS One, 5 volumes, can be obtained by the methods described in the e9685. Further, "hsa-miR-3131" takes a hairpin-like structure "hsa-mir-3131" (miRBase Accession No.MI0014151, SEQ ID NO: 255) is known as its precursor.
[0155]
The term as used herein, "hsa-miR-4463 gene" or "hsa-miR-4463" is, hsa-miR-4463 gene described in SEQ ID NO: 81 (miRBase Accession No.MIMAT0018987) and other species It encompasses such homologs or orthologs. hsa-miR-4463 gene, Jima DD, et al., 2010, Blood, 116 volumes, can be obtained by the methods described in the e118-e127. Further, "hsa-miR-4463" takes a hairpin-like structure "hsa-mir-4463" (miRBase Accession No.MI0016811, SEQ ID NO: 256) is known as its precursor.
[0156]
The term as used herein, "hsa-miR-3185 gene" or "hsa-miR-3185" is, hsa-miR-3185 gene described in SEQ ID NO: 82 (miRBase Accession No.MIMAT0015065) and other species It encompasses such homologs or orthologs. hsa-miR-3185 gene, Stark MS, et al., 2010, PLoS One, 5 volumes, can be obtained by the methods described in the e9685. Further, "hsa-miR-3185" takes a hairpin-like structure "hsa-mir-3185" (miRBase Accession No.MI0014227, SEQ ID NO: 257) is known as its precursor.
[0157]
The term as used herein, "hsa-miR-6870-5p gene" or "hsa-miR-6870-5p" is, hsa-miR-6870-5p gene (miRBase Accession described in SEQ ID NO: 83 No. MIMAT0027640) and other, including such species homologs or orthologs. hsa-miR-6870-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6870-5p" takes a hairpin-like structure "hsa-mir-6870" (miRBase Accession No.MI0022717, SEQ ID NO: 258) is known as its precursor.
[0158]
The term as used herein, "hsa-miR-6779-5p gene" or "hsa-miR-6779-5p" is, hsa-miR-6779-5p gene (miRBase Accession described in SEQ ID NO: 84 No. MIMAT0027458) and other, including such species homologs or orthologs. hsa-miR-6779-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6779-5p" takes a hairpin-like structure "hsa-mir-6779" (miRBase Accession No.MI0022624, SEQ ID NO: 259) is known as its precursor.
[0159]
The term as used herein, "hsa-miR-1273g-3p gene" or "hsa-miR-1273g-3p" is, hsa-miR-1273g-3p gene described in SEQ ID NO: 85 (miRBase Accession No. MIMAT0022742) and other, including such species homologs or orthologs. hsa-miR-1273g-3p genes, it is possible to obtain Reshmi G, et al., 2011, Genomics, 97 vol., by the method described in p333-340. Further, "hsa-miR-1273g-3p" takes a hairpin-like structure "hsa-mir-1273g" (miRBase Accession No.MI0018003, SEQ ID NO: 260) is known as its precursor.
[0160]
The term as used herein, "hsa-miR-8059 gene" or "hsa-miR-8059" is, hsa-miR-8059 gene described in SEQ ID NO: 86 (miRBase Accession No.MIMAT0030986) and other species It encompasses such homologs or orthologs. hsa-miR-8059 gene, Wang HJ, et al., 2013, Shock, 39 vol, may be obtained by the method described in p480-487. Further, "hsa-miR-8059" takes a hairpin-like structure "hsa-mir-8059" (miRBase Accession No.MI0025895, SEQ ID NO: 261) is known as its precursor.
[0161]
The term as used herein, "hsa-miR-4697-5p gene" or "hsa-miR-4697-5p" is, hsa-miR-4697-5p gene (miRBase Accession described in SEQ ID NO: 87 No. MIMAT0019791) and other, including such species homologs or orthologs. hsa-miR-4697-5p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4697-5p" takes a hairpin-like structure "hsa-mir-4697" (miRBase Accession No.MI0017330, SEQ ID NO: 262) is known as its precursor.
[0162]
The term as used herein, "hsa-miR-4674 gene" or "hsa-miR-4674" is, hsa-miR-4674 gene described in SEQ ID NO: 88 (miRBase Accession No.MIMAT0019756) and other species It encompasses such homologs or orthologs. hsa-miR-4674 gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4674" takes a hairpin-like structure "hsa-mir-4674" (miRBase Accession No.MI0017305, SEQ ID NO: 263) is known as its precursor.
[0163]
The term as used herein, "hsa-miR-4433-3p gene" or "hsa-miR-4433-3p" is, hsa-miR-4433-3p gene (miRBase Accession described in SEQ ID NO: 89 No. MIMAT0018949) and other, including such species homologs or orthologs. hsa-miR-4433-3p gene, Jima DD, et al., 2010, Blood, 116 volumes, can be obtained by the methods described in the e118-e127. Further, "hsa-miR-4433-3p" takes a hairpin-like structure "hsa-mir-4433" (miRBase Accession No.MI0016773, SEQ ID NO: 264) is known as its precursor.
[0164]
The term as used herein, "hsa-miR-4257 gene" or "hsa-miR-4257" is, hsa-miR-4257 gene described in SEQ ID NO: 90 (miRBase Accession No.MIMAT0016878) and other species It encompasses such homologs or orthologs. hsa-miR-4257 gene can be obtained Goff LA et al., 2009, PLoS One, 4 vol., by the method described in e7192. Further, "hsa-miR-4257" takes a hairpin-like structure "hsa-mir-4257" (miRBase Accession No.MI0015856, SEQ ID NO: 265) is known as its precursor.
[0165]
The term as used herein, "hsa-miR-1915-5p gene" or "hsa-miR-1915-5p" is, hsa-miR-1915-5p gene (miRBase Accession described in SEQ ID NO: 91 No. MIMAT0007891) and other, including such species homologs or orthologs. hsa-miR-1915-5p gene, Bar M et al., 2008, Stem The Cells, 26 vol, may be obtained by the method described in p2496-2505. Further, "hsa-miR-1915-5p" takes a hairpin-like structure "hsa-mir-1915" (miRBase Accession No.MI0008336, SEQ ID NO: 266) is known as its precursor.
[0166]
The term as used herein, "hsa-miR-4417 gene" or "hsa-miR-4417" is, hsa-miR-4417 gene described in SEQ ID NO: 92 (miRBase Accession No.MIMAT0018929) and other species It encompasses such homologs or orthologs. hsa-miR-4417 gene, Jima DD et al., 2010, Blood, 116 vol, may be obtained by the method described in e118-e127. Further, "hsa-miR-4417" takes a hairpin-like structure "hsa-mir-4417" (miRBase Accession No.MI0016753, SEQ ID NO: 267) is known as its precursor.
[0167]
The term as used herein, "hsa-miR-1343-5p gene" or "hsa-miR-1343-5p" is, hsa-miR-1343-5p gene (miRBase Accession described in SEQ ID NO: 93 No. MIMAT0027038) and other, including such species homologs or orthologs. hsa-miR-1343-5p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-1343-5p" takes a hairpin-like structure "hsa-mir-1343" (miRBase Accession No.MI0017320, SEQ ID NO: 182) is known as its precursor.
[0168]
The term as used herein, "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" is, hsa-miR-6781-5p gene (miRBase Accession described in SEQ ID NO: 94 No. MIMAT0027462) and other, including such species homologs or orthologs. hsa-miR-6781-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6781-5p" takes a hairpin-like structure "hsa-mir-6781" (miRBase Accession No.MI0022626, SEQ ID NO: 268) is known as its precursor.
[0169]
The term as used herein, "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" is, hsa-miR-4695-5p gene (miRBase Accession described in SEQ ID NO: 95 No. MIMAT0019788) and other, including such species homologs or orthologs. hsa-miR-4695-5p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4695-5p" takes a hairpin-like structure "hsa-mir-4695" (miRBase Accession No.MI0017328, SEQ ID NO: 269) is known as its precursor.
[0170]
The term as used herein, "hsa-miR-1237-5p gene" or "hsa-miR-1237-5p" is, hsa-miR-1237-5p gene (miRBase Accession described in SEQ ID NO: 96 No. MIMAT0022946) and other, including such species homologs or orthologs. hsa-miR-1237-5p gene, Berezikov E et al., 2007, MoI the Cell, 28 vol, may be obtained by the method described in p328-336. Further, "hsa-miR-1237-5p" takes a hairpin-like structure "hsa-mir-1237" (miRBase Accession No.MI0006327, SEQ ID NO: 270) is known as its precursor.
[0171]
The term as used herein, "hsa-miR-6775-5p gene" or "hsa-miR-6775-5p" is, hsa-miR-6775-5p gene (miRBase Accession described in SEQ ID NO: 97 No. MIMAT0027450) and other, including such species homologs or orthologs. hsa-miR-6775-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6775-5p" takes a hairpin-like structure "hsa-mir-6775" (miRBase Accession No.MI0022620, SEQ ID NO: 271) is known as its precursor.
[0172]
The term as used herein, "hsa-miR-7845-5p gene" or "hsa-miR-7845-5p" is, hsa-miR-7845-5p gene (miRBase Accession described in SEQ ID NO: 98 No. MIMAT0030420) and other, including such species homologs or orthologs. hsa-miR-7845-5p gene, it is possible to obtain Ple H, et al., 2012, PLoS One, 7 vol., by the method described in e50746. Further, "hsa-miR-7845-5p" takes a hairpin-like structure "hsa-mir-7845" (miRBase Accession No.MI0025515, SEQ ID NO: 272) is known as its precursor.
[0173]
The term as used herein, "hsa-miR-4746-3p gene" or "hsa-miR-4746-3p" is, hsa-miR-4746-3p gene (miRBase Accession described in SEQ ID NO: 99 No. MIMAT0019881) and other, including such species homologs or orthologs. hsa-miR-4746-3p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4746-3p" takes a hairpin-like structure "hsa-mir-4746" (miRBase Accession No.MI0017385, SEQ ID NO: 273) is known as its precursor.
[0174]
The term as used herein, "hsa-miR-7641 gene" or "hsa-miR-7641" is, hsa-miR-7641 gene described in SEQ ID NO: 100 (miRBase Accession No.MIMAT0029782) and other species It encompasses such homologs or orthologs. hsa-miR-7641 gene, Yoo JK et al., 2013, Arch Pharm Res, 36 vol., can be obtained by the method described in p353-358. In addition, "hsa-miR-7641" takes a hairpin-like structure as its precursor "hsa-mir-7641-1, hsa-mir-7641-2" (miRBase Accession No.MI0024975, MI0024976, SEQ ID NO: 274, 275) is known.
[0175]
The term as used herein, "hsa-miR-7847-3p gene" or "hsa-miR-7847-3p" is, hsa-miR-7847-3p gene (miRBase Accession described in SEQ ID NO: 101 No. MIMAT0030422) and other, including such species homologs or orthologs. hsa-miR-7847-3p gene, it is possible to obtain Ple H, et al., 2012, PLoS One, 7 vol., by the method described in e50746. Further, "hsa-miR-7847-3p" takes a hairpin-like structure "hsa-mir-7847" (miRBase Accession No.MI0025517, SEQ ID NO: 276) is known as its precursor.
[0176]
The term as used herein, "hsa-miR-6806-5p gene" or "hsa-miR-6806-5p" is, hsa-miR-6806-5p gene (miRBase Accession described in SEQ ID NO: 102 No. MIMAT0027512) and other, including such species homologs or orthologs. hsa-miR-6806-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6806-5p" takes a hairpin-like structure "hsa-mir-6806" (miRBase Accession No.MI0022651, SEQ ID NO: 277) is known as its precursor.
[0177]
The term as used herein, "hsa-miR-4467 gene" or "hsa-miR-4467" is, hsa-miR-4467 gene described in SEQ ID NO: 103 (miRBase Accession No.MIMAT0018994) and other species It encompasses such homologs or orthologs. hsa-miR-4467 gene, Jima DD et al., 2010, Blood, 116 vol, may be obtained by the method described in e118-e127. Further, "hsa-miR-4467" takes a hairpin-like structure "hsa-mir-4467" (miRBase Accession No.MI0016818, SEQ ID NO: 278) is known as its precursor.
[0178]
The term as used herein, "hsa-miR-4726-5p gene" or "hsa-miR-4726-5p" is, hsa-miR-4726-5p gene (miRBase Accession described in SEQ ID NO: 104 No. MIMAT0019845) and other, including such species homologs or orthologs. hsa-miR-4726-5p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4726-5p" takes a hairpin-like structure "hsa-mir-4726" (miRBase Accession No.MI0017363, SEQ ID NO: 279) is known as its precursor.
[0179]
The term as used herein, "hsa-miR-4648 gene" or "hsa-miR-4648" is, hsa-miR-4648 gene described in SEQ ID NO: 105 (miRBase Accession No.MIMAT0019710) and other species It encompasses such homologs or orthologs. hsa-miR-4648 gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4648" takes a hairpin-like structure "hsa-mir-4648" (miRBase Accession No.MI0017275, SEQ ID NO: 280) is known as its precursor.
[0180]
The term as used herein, "hsa-miR-6089 gene" or "hsa-miR-6089" is, hsa-miR-6089 gene described in SEQ ID NO: 106 (miRBase Accession No.MIMAT0023714) and other species It encompasses such homologs or orthologs. hsa-miR-6089 gene can be obtained Yoo JK et al., 2012, Stem Cells Dev, 21 vol., by the method described in p2049-2057. In addition, "hsa-miR-6089" takes a hairpin-like structure as its precursor "hsa-mir-6089-1, hsa-mir-6089-2" (miRBase Accession No.MI0020366, MI0023563, SEQ ID NO: 281, 282) is known.
[0181]
The term as used herein, "hsa-miR-1260b gene" or "hsa-miR-1260b" is, hsa-miR-1260b gene described in SEQ ID NO: 107 (miRBase Accession No.MIMAT0015041) and other species It encompasses such homologs or orthologs. hsa-miR-1260b gene, Stark MS, et al., 2010, PLoS One, 5 volumes, can be obtained by the methods described in the e9685. Further, "hsa-miR-1260b" takes a hairpin-like structure "hsa-mir-1260b" (miRBase Accession No.MI0014197, SEQ ID NO: 283) is known as its precursor.
[0182]
The term as used herein, "hsa-miR-4532 gene" or "hsa-miR-4532" is, hsa-miR-4532 gene described in SEQ ID NO: 108 (miRBase Accession No.MIMAT0019071) and other species It encompasses such homologs or orthologs. hsa-miR-4532 gene, Jima DD et al., 2010, Blood, 116 vol, may be obtained by the method described in e118-e127. Further, "hsa-miR-4532" takes a hairpin-like structure "hsa-mir-4532" (miRBase Accession No.MI0016899, SEQ ID NO: 284) is known as its precursor.
[0183]
The term as used herein, "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" is, hsa-miR-5195-3p gene (miRBase Accession described in SEQ ID NO: 109 No. MIMAT0021127) and other, including such species homologs or orthologs. hsa-miR-5195-3p gene can be obtained Schotte D et al., 2011, Leukemia, 25 vol., by the method described in p1389-1399. Further, "hsa-miR-5195-3p" takes a hairpin-like structure "hsa-mir-5195" (miRBase Accession No.MI0018174, SEQ ID NO: 285) is known as its precursor.
[0184]
The term as used herein, "hsa-miR-3188 gene" or "hsa-miR-3188" is, hsa-miR-3188 gene described in SEQ ID NO: 110 (miRBase Accession No.MIMAT0015070) and other species It encompasses such homologs or orthologs. hsa-miR-3188 gene, Stark MS, et al., 2010, PLoS One, 5 volumes, can be obtained by the methods described in the e9685. Further, "hsa-miR-3188" takes a hairpin-like structure "hsa-mir-3188" (miRBase Accession No.MI0014232, SEQ ID NO: 286) is known as its precursor.
[0185]
The term as used herein, "hsa-miR-6848-5p gene" or "hsa-miR-6848-5p" is, hsa-miR-6848-5p gene (miRBase Accession described in SEQ ID NO: 111 No. MIMAT0027596) and other, including such species homologs or orthologs. hsa-miR-6848-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6848-5p" takes a hairpin-like structure "hsa-mir-6848" (miRBase Accession No.MI0022694, SEQ ID NO: 287) is known as its precursor.
[0186]
The term as used herein, "hsa-miR-1233-5p gene" or "hsa-miR-1233-5p" is, hsa-miR-1233-5p gene (miRBase Accession described in SEQ ID NO: 112 No. MIMAT0022943) and other, including such species homologs or orthologs. hsa-miR-1233-5p gene, Berezikov E et al., 2007, MoI the Cell, 28 vol, may be obtained by the method described in p328-336. In addition, "hsa-miR-1233-5p" takes a hairpin-like structure as its precursor "hsa-mir-1233-1, hsa-mir-1233-2" (miRBase Accession No.MI0006323, MI0015973, SEQ ID NO: 288, 289) is known.
[0187]
The term as used herein, "hsa-miR-6717-5p gene" or "hsa-miR-6717-5p" is, hsa-miR-6717-5p gene (miRBase Accession described in SEQ ID NO: 113 No. MIMAT0025846) and other, including such species homologs or orthologs. hsa-miR-6717-5p gene, Li Y-et al., 2012, Gene, 497 vol, may be obtained by the method described in p330-335. Further, "hsa-miR-6717-5p" takes a hairpin-like structure "hsa-mir-6717" (miRBase Accession No.MI0022551, SEQ ID NO: 290) is known as its precursor.
[0188]
The term as used herein, "hsa-miR-3195 gene" or "hsa-miR-3195" is, hsa-miR-3195 gene described in SEQ ID NO: 114 (miRBase Accession No.MIMAT0015079) and other species It encompasses such homologs or orthologs. hsa-miR-3195 gene, Stark MS, et al., 2010, PLoS One, 5 volumes, can be obtained by the methods described in the e9685. Further, "hsa-miR-3195" takes a hairpin-like structure "hsa-mir-3195" (miRBase Accession No.MI0014240, SEQ ID NO: 291) is known as its precursor.
[0189]
The term as used herein, "hsa-miR-6757-5p gene" or "hsa-miR-6757-5p" is, hsa-miR-6757-5p gene (miRBase Accession described in SEQ ID NO: 115 No. MIMAT0027414) and other, including such species homologs or orthologs. hsa-miR-6757-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6757-5p" takes a hairpin-like structure "hsa-mir-6757" (miRBase Accession No.MI0022602, SEQ ID NO: 292) is known as its precursor.
[0190]
The term as used herein, "hsa-miR-8072 gene" or "hsa-miR-8072" is, hsa-miR-8072 gene described in SEQ ID NO: 116 (miRBase Accession No.MIMAT0030999) and other species It encompasses such homologs or orthologs. hsa-miR-8072 gene, Wang HJ, et al., 2013, Shock, 39 vol, may be obtained by the method described in p480-487. Further, "hsa-miR-8072" takes a hairpin-like structure "hsa-mir-8072" (miRBase Accession No.MI0025908, SEQ ID NO: 293) is known as its precursor.
[0191]
The term as used herein, "hsa-miR-4745-5p gene" or "hsa-miR-4745-5p" is, hsa-miR-4745-5p gene (miRBase Accession described in SEQ ID NO: 117 No. MIMAT0019878) and other, including such species homologs or orthologs. hsa-miR-4745-5p gene can be obtained Persson H et al., 2011,. Cancer Res, 71 vol., by the method described in p78-86. Further, "hsa-miR-4745-5p" takes a hairpin-like structure "hsa-mir-4745" (miRBase Accession No.MI0017384, SEQ ID NO: 294) is known as its precursor.
[0192]
The term as used herein, "hsa-miR-6511a-5p gene" or "hsa-miR-6511a-5p" is, hsa-miR-6511a-5p gene described in SEQ ID NO: 118 (miRBase Accession No. MIMAT0025478) and other, including such species homologs or orthologs. hsa-miR-6511a-5p gene, Joyce CE, et al., 2011, Hum Mol Genet, 20 volumes, can be obtained by the methods described in p4025-4040. In addition, "hsa-miR-6511a-5p" is, take a hairpin-like structure as its precursor "hsa-mir-6511a-1, hsa-mir-6511a-2, hsa-mir-6511a-3, hsa-mir -6511a-4 "(miRBase Accession No.MI0022223, MI0023564, MI0023565, MI0023566, SEQ ID NO: 295,296,297,298) is known.
[0193]
The term as used herein, "hsa-miR-6776-5p gene" or "hsa-miR-6776-5p" is, hsa-miR-6776-5p gene (miRBase Accession described in SEQ ID NO: 119 No. MIMAT0027452) and other, including such species homologs or orthologs. hsa-miR-6776-5p gene can be obtained Ladewig E et al., 2012, Genome Res, 22 vol., by the method described in p1634-1645. Further, "hsa-miR-6776-5p" takes a hairpin-like structure "hsa-mir-6776" (miRBase Accession No.MI0022621, SEQ ID NO: 299) is known as its precursor.
[0194]
The term as used herein, "hsa-miR-371a-5p gene" or "hsa-miR-371a-5p" is, hsa-miR-371a-5p gene described in SEQ ID NO: 120 (miRBase Accession No. MIMAT0004687) and other, including such species homologs or orthologs. hsa-miR-371a-5p gene, Suh MR et al., 2004, Dev Biol, 270 vol, may be obtained by the method described in p488-498. Further, "hsa-miR-371a-5p" takes a hairpin-like structure "hsa-mir-371a" (miRBase Accession No.MI0000779, SEQ ID NO: 300) is known as its precursor.
[0195]
The term as used herein, "hsa-miR-1227-5p gene" or "hsa-miR-1227-5p" is, hsa-miR-1227-5p gene (miRBase Accession described in SEQ ID NO: 121 No. MIMAT0022941) and other, including such species homologs or orthologs. hsa-miR-1227-5p gene, Berezikov E et al., 2007, MoI the Cell, 28 vol, may be obtained by the method described in p328-336. Further, "hsa-miR-1227-5p" takes a hairpin-like structure "hsa-mir-1227" (miRBase Accession No.MI0006316, SEQ ID NO: 301) is known as its precursor.
[0196]
The term as used herein, "hsa-miR-7150 gene" or "hsa-miR-7150" is, hsa-miR-7150 gene described in SEQ ID NO: 122 (miRBase Accession No.MIMAT0028211) and other species It encompasses such homologs or orthologs. hsa-miR-7150 gene, Oulas A et al., 2009, Nucleic Acids Res, 37 vol., can be obtained by the method described in p3276-3287. Further, "hsa-miR-7150" takes a hairpin-like structure "hsa-mir-7150" (miRBase Accession No.MI0023610, SEQ ID NO: 302) is known as its precursor.
[0197]
The term as used herein, "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" is, hsa-miR-1915-3p gene (miRBase Accession described in SEQ ID NO: 123 No. MIMAT0007892) and other, including such species homologs or orthologs. hsa-miR-1915-3p gene, Bar M et al., 2008, Stem The Cells, 26 vol, may be obtained by the method described in p2496-2505. Further, "hsa-miR-1915-3p" takes a hairpin-like structure "hsa-mir-1915" (miRBase Accession No.MI0008336, SEQ ID NO: 266) is known as its precursor.
[0198]
The term as used herein, "hsa-miR-187-5p gene" or "hsa-miR-187-5p" is, hsa-miR-187-5p gene (miRBase Accession described in SEQ ID NO: 124 No. MIMAT0004561) and other, including such species homologs or orthologs. hsa-miR-187-5p gene, Lim LP, et al., 2003, Science, 299 vol, may be obtained by the method described in p1540. Further, "hsa-miR-187-5p" takes a hairpin-like structure "hsa-mir-187" (miRBase Accession No.MI0000274, SEQ ID NO: 303) is known as its precursor.
[0199]
The term as used herein, "hsa-miR-614 gene" or "hsa-miR-614" is, hsa-miR-614 gene described in SEQ ID NO: 125 (miRBase Accession No.MIMAT0003282) and other species It encompasses such homologs or orthologs. hsa-miR-614 gene, Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103 vol, may be obtained by the method described in p3687-3692. Further, "hsa-miR-614" takes a hairpin-like structure "hsa-mir-614" (miRBase Accession No.MI0003627, SEQ ID NO: 304) is known as its precursor.
[0200]
The term as used herein, "hsa-miR-19b-3p gene" or "hsa-miR-19b-3p" is, hsa-miR-19b-3p gene described in SEQ ID NO: 126 (miRBase Accession No. MIMAT0000074) and other, including such species homologs or orthologs. hsa-miR-19b-3p genes, Lagos-Quintana M et al., 2001, Science, 294 vol, may be obtained by the method described in p853-858. In addition, "hsa-miR-19b-3p" is, take a hairpin-like structure as its precursor "hsa-mir-19b-1, hsa-mir-19b-2" (miRBase Accession No.MI0000074, MI0000075, SEQ ID NO: 305 and 306) are known.
[0201]
The term as used herein, "hsa-miR-1225-5p gene" or "hsa-miR-1225-5p" is, hsa-miR-1225-5p gene (miRBase Accession described in SEQ ID NO: 127 No. MIMAT0005572) and other, including such species homologs or orthologs. hsa-miR-1225-5p gene, Berezikov E et al., 2007, MoI the Cell, 28 vol, may be obtained by the method described in p328-336. Further, "hsa-miR-1225-5p" takes a hairpin-like structure "hsa-mir-1225" (miRBase Accession No.MI0006311, SEQ ID NO: 307) is known as its precursor.
[0202]
The term as used herein, "hsa-miR-451a gene" or "hsa-miR-451a" is, hsa-miR-451a gene described in SEQ ID NO: 128 (miRBase Accession No.MIMAT0001631) and other species It encompasses such homologs or orthologs. hsa-miR-451a gene can be obtained Altuvia Y et al., 2005, Nucleic Acids Res, 33 vol, by the method described in p2697-2706. Further, "hsa-miR-451a" takes a hairpin-like structure "hsa-mir-451a" (miRBase Accession No.MI0001729, SEQ ID NO: 308) is known as its precursor.
The scope of the claims
[Claim 1]
肺 が ん マ ー カ ー で あ る, miR-6768-5p, miR-6836-3p, miR-6782-5p, miR-3663-3p, miR-1908-3p, miR-6726-5p, miR-4258, miR-1343-3p , miR-4516, miR-6875-5p, miR-4651, miR-6825-5p, miR-6840-3p, miR-6780b-5p, miR-6749-5p, miR-8063, miR-6784-5p, miR -3679-5p, miR-3184-5p, miR-663b, miR-6880-5p, miR-1908-5p, miR-92a-2-5p, miR-7975, miR-7110-5p, miR-6842-5p , miR-6857-5p, miR-5572, miR-3197, miR-6131, miR-6889-5p, miR-4454, miR-1199-5p, miR-1247-3p, miR-6800-5p, miR-6872 3P, miR-4649-5p, miR-6791-5p, miR-4433b-3p, miR-3135b, miR-128-2-5p, miR-4675, miR-4472, miR-6785-5p, miR-6741 -5p, miR-7977, miR-3665, miR-128-1-5p, miR-4286, miR-6765-3p, miR-4632-5p, miR-365a-5p, miR-6088, miR-6816-5p , miR-6885-5p, miR-711, miR-6765-5p, miR-3180, miR-4442, miR-4792, miR-6721-5p, miR-6798-5p, miR-3162-5p, miR-6126 , miR-4758-5p, miR-2392, miR-486-3p, miR-6727-5p, miR-4728-5p, miR-6746-5p, miR-4270, miR-3940-5p, miR-4725-3p , miR-7108-5p, miR-3656, miR-6879-5p, miR-6738-5p, miR-1260a, miR-4446-3p, miR-3131, miR-4463, miR-3185, miR-6870-5p , miR-6779-5p, miR-1273g-3p, miR-8059, miR-4697-5p, miR-4674, miR-4433-3p, miR-4257, miR-1915-5p, miR-4417, miR-1343 -5p, miR-6781-5p, miR-4695-5p, miR-1237-5p, miR-6775-5p, miR-7845-5p, miR-4746-3p, miR-7641, miR-7847-3p, miR -6806-5p, miR-4467, miR-4726-5p, miR-4648, miR-6089, miR-1260b, miR-4532, miR-5195-3p, miR-3188, miR-6848-5p, miR-1233 -5p, miR-6717-5p, miR-3195, miR-6757-5p, miR-8072, miR-4745-5p, miR-6511a-5p, miR-6776-5p, miR-371a-5p, miR-1227 -5p, miR-7150, miR-1915-3p, miR-187-5p, miR-614, miR-1225-5p, miR-451a, miR-939-5p, miR-223-3p, miR-125a-3p , miR-92b-5p, miR-22-3p, miR-6073, miR-6845-5p, miR-6769b-5p, miR-4665-3p, miR-1913, miR-1228-3p, miR-940, miR -296-3p, miR-4690-5p, miR-548q, miR-663a, miR-1249, miR-1202, miR-7113-3p, miR-1225-3p, miR-4783-3p, miR-4448 及 び miR -4534 か ら な る 群 か ら 選 択 さ れ る 少 な く と も 1 つ 以上 の ポ リ ヌ ク レ オ チ ド と 特異 的 に 結合 可能 な 核酸 を 含 む, 肺 が ん の 検 出 用 キ ッ ト.
[Claim 2]
miR-6768-5p is hsa-miR-6768-5p, miR-6836-3p is hsa-miR-6836-3p, miR-6782-5p is hsa-miR-6782-5p, miR- 3663-3p is hsa-miR-3663-3p, miR-1908-3p is hsa-miR-1908-3p, miR-6726-5p is hsa-miR-6726-5p, the miR-4258 is hsa-miR-4258, miR-1343-3p is hsa-miR-1343-3p, miR-4516 is hsa-miR-4516, miR-6875-5p is in hsa-miR-6875-5p Yes, miR-4651 is hsa-miR-4651, miR-6825-5p is hsa-miR-6825-5p, miR-6840-3p is hsa-miR-6840-3p, miR-6780b- 5p is hsa-miR-6780b-5p, miR-6749-5p is hsa-miR-6749-5p, miR-8063 is hsa-miR-8063, miR-6784-5p is hsa-miR- a 6784-5p, miR-3679-5p is hsa-miR-3679-5p, miR-3184-5p is hsa-miR-3184-5p, miR-663b is hsa-miR-663b, miR-6880-5p is hsa-miR-6880-5p, miR-1908-5p is hsa-miR-1908-5p, miR-92a-2-5p is in hsa-miR-92a-2-5p Yes, miR-7975 is hsa-miR-7975, miR-7110-5p is hsa-miR-7110-5p, miR-6842-5p is hsa-miR-6842-5p, miR-6857- 5p is hsa-miR-6857-5p, miR-5572 is hsa-miR-5572, miR-3197 is hsa-miR-3197, miR-6131 is hsa-miR-6131, miR- 6889-5p is hsa-miR-6889-5p, miR-4454 is hsa-miR-4454, miR-1199-5p is hsa-miR-1199-5p, the miR-1247-3p hsa- is a miR-1247-3p, miR-6800-5p is hsa-miR-6800-5p, miR-6872-3p is hsa-miR-6872-3p, miR-4649-5p is hsa-miR- a 4649-5p, miR-6791-5p is hsa-miR-6791-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-3135b is hsa-miR-3135b, miR-128-2-5p is hsa-miR-128-2-5p, miR-4675 is hsa-miR-4675, miR-4472 is hsa-miR-4472, is miR-6785-5p is hsa-miR-6785-5p, miR-6741-5p is hsa-miR-6741-5p, miR-7977 is hsa-miR-7977, miR-3665 is hsa-miR-3665, miR-128-1-5p is hsa-miR-128-1-5p, miR-4286 is hsa-miR-4286, miR-6765-3p is hsa-miR-6765-3p, miR- 4632-5p is hsa-miR-4632-5p, miR-365a-5p is hsa-miR-365a-5p, miR-6088 is hsa-miR-6088, is miR-6816-5p hsa- is a miR-6816-5p, miR-6885-5p is hsa-miR-6885-5p, miR-711 is hsa-miR-711, miR-6765-5p is in hsa-miR-6765-5p Yes, miR-3180 is hsa-miR-3180, miR-4442 is hsa-miR-4442, miR-4792 is hsa-miR-4792, miR-6721-5p is hsa-miR-6721- a 5p, miR-6798-5p is hsa-miR-6798-5p, miR-3162-5p is hsa-miR-3162-5p, miR-6126 is hsa-miR-6126, miR- 4758-5p is hsa-miR-4758-5p, miR-2392 is hsa-miR-2392, miR-486-3p is hsa-miR-486-3p, is miR-6727-5p hsa- is a miR-6727-5p, miR-4728-5p is hsa-miR-4728-5p, miR-6746-5p is hsa-miR-6746-5p, miR-4270 is in the hsa-miR-4270 Yes, miR-3940-5p is hsa-miR-3940-5p, miR-4725-3p is hsa-miR-4725-3p, miR-7108-5p is hsa-miR-7108-5p, miR-3656 is hsa-miR-3656, miR-6879-5p is hsa-miR-6879-5p, miR-6738-5p is hsa-miR-6738-5p, the miR-1260a hsa- is a miR-1260a, miR-4446-3p is hsa-miR-4446-3p, miR-3131 is hsa-miR-3131, miR-4463 is hsa-miR-4463, is miR-3185 is hsa-miR-3185, miR-6870-5p is hsa-miR-6870-5p, miR-6779-5p is hsa-miR-6779-5p, miR-1273g-3p is hsa-miR- a 1273g-3p, miR-8059 is hsa-miR-8059, miR-4697-5p is hsa-miR-4697-5p, miR-4674 is hsa-miR-4674, miR-4433- 3p is hsa-miR-4433-3p, miR-4257 is hsa-miR-4257, miR-1915-5p is hsa-miR-1915-5p, miR-4417 is in the hsa-miR-4417 Yes, miR-1343-5p is hsa-miR-1343-5p, miR-6781-5p is hsa-miR-6781-5p, miR-4695-5p is hsa-miR-4695-5p, miR-1237-5p is hsa-miR-1237-5p, miR-6775-5p is hsa-miR-6775-5p, miR-7845-5p is hsa-miR-7845-5p, miR- 4746-3p is hsa-miR-4746-3p, miR-7641 is hsa-miR-7641, miR-7847-3p is hsa-miR-7847-3p, the miR-6806-5p hsa- is a miR-6806-5p, miR-4467 is hsa-miR-4467, miR-4726-5p is hsa-miR-4726-5p, miR-4648 is hsa-miR-4648, miR- 6089 is hsa-miR-6089, miR-1260b is hsa-miR-1260b, miR-4532 is hsa-miR-4532, miR-5195-3p is hsa-miR-5195-3p, miR-3188 is hsa-miR-3188, miR-6848-5p is hsa-miR-6848-5p, miR-1233-5p is hsa-miR-1233-5p, the miR-6717-5p is hsa-miR-6717-5p, miR-3195 is hsa-miR-3195, miR-6757-5p is hsa-miR-6757-5p, miR-8072 is hsa-miR-8072, miR-4745-5p is hsa-miR-4745-5p, miR-6511a-5p is hsa-miR-6511a-5p, miR-6776-5p is hsa-miR-6776-5p, miR- 371a-5p is hsa-miR-371a-5p, miR-1227-5p is hsa-miR-1227-5p, miR-7150 is hsa-miR-7150, is miR-1915-3p hsa- miR-1915-3p, miR-187-5p is hsa-miR-187-5p, miR-614 is hsa-miR-614, miR-1225-5p is hsa-miR-1225-5p, miR-451a is hsa-miR-451a, miR-939-5p is hsa-miR-939-5p, miR-223-3p is hsa-miR-223-3p, the miR-125a-3p is hsa-miR-125a-3p, miR-92b-5p is hsa-miR-92b-5p, miR-22-3p is hsa-miR-22-3p, miR-6073 is hsa-miR- is 6073, miR-6845-5p is hsa-miR-6845-5p, miR-6769b-5p is hsa-miR-6769b-5p, miR-4665-3p is in hsa-miR-4665-3p Yes, miR-1913 is hsa-miR-1913, miR-1228-3p is hsa-miR-1228-3p, miR-940 is hsa-miR-940, is miR-296-3p hsa- is a miR-296-3p, miR-4690-5p is hsa-miR-4690-5p, miR-548q is hsa-miR-548q, miR-663a is hsa-miR-663a, miR- 1249 is hsa-miR-1249, miR-1202 is hsa-miR-1202, miR-7113-3p is hsa-miR-7113-3p, miR-1225-3p is hsa-miR-1225- is 3p, miR-4783-3p is hsa-miR-4783-3p, miR-4448 is hsa-miR-4448, and, miR-4534 is hsa-miR-4534, to claim 1 the kit according.
[Claim 3]
Said nucleic acid, a polynucleotide shown in the following (a) -
(e): (a) SEQ ID NO: 1 ~ 125, 127 ~ 130, 132 ~ 134, and the base sequence or represented by any one of 561-578 the nucleotide u in sequence consisting of the nucleotide sequence is t polynucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, (b) SEQ ID NOs 125 and 127 ~ 130, 132 ~ 134, and a polynucleotide comprising the nucleotide sequence represented by any one of
561-578, (c) SEQ ID NOs 125 and 127 ~ 130, 132 ~ 134, and is represented by any one of 561-578 polynucleotides, a variant thereof u in the nucleotide sequence or the nucleotide sequence consisting of a nucleotide sequence complementary to the nucleotide sequence which is t, the fragment comprising the derivative, or 15 or more contiguous bases,
(d-) SEQ ID NO: 1 ~ 125, 127 ~ 130, 132 ~ 134, and, a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence shown in any 561-578 and
( e) wherein (a) any of the polynucleotides and a polynucleotide hybridizing under stringent conditions of ~ (d),
a polynucleotide selected from the group consisting of a kit according to claim 1 or 2.
[Claim 4]
The kit is another lung markers, miR-19b-3p, at least one or more polynucleotide specifically bindable nucleic acid selected from the group consisting of miR-1228-5p and miR-1307-3p further comprising, kit according to any one of claims 1 to 3.
[Claim 5]
miR-19b-3p is hsa-miR-19b-3p, miR-1228-5p is hsa-miR-1228-5p, and, miR-1307-3p is hsa-miR-1307-3p, the kit according to claim 4.
[6.]
Said nucleic acid, a polynucleotide shown in the following
(f) From (f) the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 126 and 131 and 579 comprising polynucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, polynucleotides comprising a nucleotide sequence represented by any one of (g) SEQ ID NO: 126 and 131 and
579, (h) SEQ ID NO: 126 and 131 and 579 or u in the nucleotide sequence or the nucleotide sequence represented by consists of a nucleotide sequence complementary to the nucleotide sequence is t polynucleotide, its variants, derivatives thereof, or more than 15 a fragment thereof comprising a contiguous bases,
polynucleotides comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (i) SEQ ID NO: 126 and 131 and 579, and
(j) wherein (f) ~ any polynucleotide and a polynucleotide hybridizing under stringent conditions (i), a polynucleotide selected from the group consisting of claim 4 or 5, kit.
[7.]
The kit is another of lung cancer markers, miR-4271, miR-642b-3p, miR-6075, miR-6125, miR-887-3p, miR-6851-5p, miR-6763-5p, miR-3928 -3p, miR-4443, miR-3648, miR-149-3p, miR-4689, miR-4763-3p, miR-6729-5p, miR-3196, miR-8069, miR-1268a, miR-4739, miR -1268b, miR-5698, miR-6752-5p, miR-4507, miR-564, miR-4497, miR-6877-5p, miR-6087, miR-4731-5p, miR-615-5p, miR-760 , miR-6891-5p, miR-6887-5p, miR-4525, miR-1914-3p, miR-619-5p, miR-5001-5p, miR-6722-3p, miR-3621, miR-4298, miR -675-5p and further comprising at least one polynucleotide capable of specifically binding nucleic acid is selected from the group consisting of miR-4655-5p, kit according to any one of claims 1 to 6 .
[8.]
miR-4271 is hsa-miR-4271, miR-642b-3p is hsa-miR-642b-3p, miR-6075 is hsa-miR-6075, miR-6125 is in the hsa-miR-6125 Yes, miR-887-3p is hsa-miR-887-3p, miR-6851-5p is hsa-miR-6851-5p, miR-6763-5p is hsa-miR-6763-5p, miR-3928-3p is hsa-miR-3928-3p, miR-4443 is hsa-miR-4443, miR-3648 is hsa-miR-3648, miR-149-3p is hsa-miR- a 149-3p, miR-4689 is hsa-miR-4689, miR-4763-3p is hsa-miR-4763-3p, miR-6729-5p is hsa-miR-6729-5p, miR-3196 is hsa-miR-3196, miR-8069 is hsa-miR-8069, miR-1268a is hsa-miR-1268a, miR-4739 is hsa-miR-4739, miR- 1268b is hsa-miR-1268b, miR-5698 is hsa-miR-5698, miR-6752-5p is hsa-miR-6752-5p, miR-4507 is hsa-miR-4507, miR-564 is hsa-miR-564, miR-4497 is hsa-miR-4497, miR-6877-5p is hsa-miR-6877-5p, miR-6087 is in the hsa-miR-6087 Yes, miR-4731-5p is hsa-miR-4731-5p, miR-615-5p is hsa-miR-615-5p, miR-760 is hsa-miR-760, miR-6891- 5p is hsa-miR-6891-5p, miR-6887-5p is hsa-miR-6887-5p, miR-4525 is hsa-miR-4525, miR-1914-3p is hsa-miR- a 1914-3p, miR-619-5p is hsa-miR-619-5p, miR-5001-5p is hsa-miR-5001-5p, miR-6722-3p is hsa-miR-6722- is 3p, miR-3621 is hsa-miR-3621, miR-4298 is hsa-miR-4298, miR-675-5p is hsa-miR-675-5p, and, miR-4655- 5p is hsa-miR-4655-5p, kit according to claim 7.
[9.]
Said nucleic acid, the following (k) a polynucleotide shown in ~ (o):
(k) Poly u in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 135 ~ 174 consisting of a nucleotide sequence which is at t nucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, polynucleotides comprising a nucleotide sequence represented by any of (l) SEQ ID NO: 135 to
174, (yd) SEQ ID NO: 135 ~ polynucleotides u in the nucleotide sequence or the nucleotide sequence represented by any one of 174 consisting of a nucleotide sequence complementary to the nucleotide sequence which is t, a variant thereof, the derivatives thereof, or 15 or more contiguous bases fragment,
a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence that u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 135-174, and
(o) the (k) any polynucleotide under stringent conditions with a polynucleotide hybridizing of ~ (n),
is a polynucleotide selected from the group consisting of a kit according to claim 7 or 8.
[10.]
The kit comprises at least two or more nucleic acids respectively capable of specifically binding at least two or more polynucleotides selected from all lung marker according to claim 1 or 2, claims 1 to 9, the kit according to any one of.
[11.]
肺 が ん マ ー カ ー で あ る, miR-6768-5p, miR-6836-3p, miR-6782-5p, miR-3663-3p, miR-1908-3p, miR-6726-5p, miR-4258, miR-1343-3p , miR-4516, miR-6875-5p, miR-4651, miR-6825-5p, miR-6840-3p, miR-6780b-5p, miR-6749-5p, miR-8063, miR-6784-5p, miR -3679-5p, miR-3184-5p, miR-663b, miR-6880-5p, miR-1908-5p, miR-92a-2-5p, miR-7975, miR-7110-5p, miR-6842-5p , miR-6857-5p, miR-5572, miR-3197, miR-6131, miR-6889-5p, miR-4454, miR-1199-5p, miR-1247-3p, miR-6800-5p, miR-6872 3P, miR-4649-5p, miR-6791-5p, miR-4433b-3p, miR-3135b, miR-128-2-5p, miR-4675, miR-4472, miR-6785-5p, miR-6741 -5p, miR-7977, miR-3665, miR-128-1-5p, miR-4286, miR-6765-3p, miR-4632-5p, miR-365a-5p, miR-6088, miR-6816-5p , miR-6885-5p, miR-711, miR-6765-5p, miR-3180, miR-4442, miR-4792, miR-6721-5p, miR-6798-5p, miR-3162-5p, miR-6126 , miR-4758-5p, miR-2392, miR-486-3p, miR-6727-5p, miR-4728-5p, miR-6746-5p, miR-4270, miR-3940-5p, miR-4725-3p , miR-7108-5p, miR-3656, miR-6879-5p, miR-6738-5p, miR-1260a, miR-4446-3p, miR-3131, miR-4463, miR-3185, miR-6870-5p , miR-6779-5p, miR-1273g-3p, miR-8059, miR-4697-5p, miR-4674, miR-4433-3p, miR-4257, miR-1915-5p, miR-4417, miR-1343 -5p, miR-6781-5p, miR-4695-5p, miR-1237-5p, miR-6775-5p, miR-7845-5p, miR-4746-3p, miR-7641, miR-7847-3p, miR -6806-5p, miR-4467, miR-4726-5p, miR-4648, miR-6089, miR-1260b, miR-4532, miR-5195-3p, miR-3188, miR-6848-5p, miR-1233 -5p, miR-6717-5p, miR-3195, miR-6757-5p, miR-8072, miR-4745-5p, miR-6511a-5p, miR-6776-5p, miR-371a-5p, miR-1227 -5p, miR-7150, miR-1915-3p, miR-187-5p, miR-614, miR-1225-5p, miR-451a, miR-939-5p, miR-223-3p, miR-125a-3p , miR-92b-5p, miR-22-3p, miR-6073, miR-6845-5p, miR-6769b-5p, miR-4665-3p, miR-1913, miR-1228-3p, miR-940, miR -296-3p, miR-4690-5p, miR-548q, miR-663a, miR-1249, miR-1202, miR-7113-3p, miR-1225-3p, miR-4783-3p, miR-4448 及 び miR -4534 か ら な る 群 か ら 選 択 さ れ る 少 な く と も 1 つ 以上 の ポ リ ヌ ク レ オ チ ド と 特異 的 に 結合 可能 な 核酸 を 含 む, 肺 が ん の 検 出 用 デ バ イ ス.
[12.]
miR-6768-5p is hsa-miR-6768-5p, miR-6836-3p is hsa-miR-6836-3p, miR-6782-5p is hsa-miR-6782-5p, miR- 3663-3p is hsa-miR-3663-3p, miR-1908-3p is hsa-miR-1908-3p, miR-6726-5p is hsa-miR-6726-5p, the miR-4258 is hsa-miR-4258, miR-1343-3p is hsa-miR-1343-3p, miR-4516 is hsa-miR-4516, miR-6875-5p is in hsa-miR-6875-5p Yes, miR-4651 is hsa-miR-4651, miR-6825-5p is hsa-miR-6825-5p, miR-6840-3p is hsa-miR-6840-3p, miR-6780b- 5p is hsa-miR-6780b-5p, miR-6749-5p is hsa-miR-6749-5p, miR-8063 is hsa-miR-8063, miR-6784-5p is hsa-miR- a 6784-5p, miR-3679-5p is hsa-miR-3679-5p, miR-3184-5p is hsa-miR-3184-5p, miR-663b is hsa-miR-663b, miR-6880-5p is hsa-miR-6880-5p, miR-1908-5p is hsa-miR-1908-5p, miR-92a-2-5p is in hsa-miR-92a-2-5p Yes, miR-7975 is hsa-miR-7975, miR-7110-5p is hsa-miR-7110-5p, miR-6842-5p is hsa-miR-6842-5p, miR-6857- 5p is hsa-miR-6857-5p, miR-5572 is hsa-miR-5572, miR-3197 is hsa-miR-3197, miR-6131 is hsa-miR-6131, miR- 6889-5p is hsa-miR-6889-5p, miR-4454 is hsa-miR-4454, miR-1199-5p is hsa-miR-1199-5p, the miR-1247-3p hsa- is a miR-1247-3p, miR-6800-5p is hsa-miR-6800-5p, miR-6872-3p is hsa-miR-6872-3p, miR-4649-5p is hsa-miR- a 4649-5p, miR-6791-5p is hsa-miR-6791-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-3135b is hsa-miR-3135b, miR-128-2-5p is hsa-miR-128-2-5p, miR-4675 is hsa-miR-4675, miR-4472 is hsa-miR-4472, is miR-6785-5p is hsa-miR-6785-5p, miR-6741-5p is hsa-miR-6741-5p, miR-7977 is hsa-miR-7977, miR-3665 is hsa-miR-3665, miR-128-1-5p is hsa-miR-128-1-5p, miR-4286 is hsa-miR-4286, miR-6765-3p is hsa-miR-6765-3p, miR- 4632-5p is hsa-miR-4632-5p, miR-365a-5p is hsa-miR-365a-5p, miR-6088 is hsa-miR-6088, is miR-6816-5p hsa- is a miR-6816-5p, miR-6885-5p is hsa-miR-6885-5p, miR-711 is hsa-miR-711, miR-6765-5p is in hsa-miR-6765-5p Yes, miR-3180 is hsa-miR-3180, miR-4442 is hsa-miR-4442, miR-4792 is hsa-miR-4792, miR-6721-5p is hsa-miR-6721- a 5p, miR-6798-5p is hsa-miR-6798-5p, miR-3162-5p is hsa-miR-3162-5p, miR-6126 is hsa-miR-6126, miR- 4758-5p is hsa-miR-4758-5p, miR-2392 is hsa-miR-2392, miR-486-3p is hsa-miR-486-3p, is miR-6727-5p hsa- is a miR-6727-5p, miR-4728-5p is hsa-miR-4728-5p, miR-6746-5p is hsa-miR-6746-5p, miR-4270 is in the hsa-miR-4270 Yes, miR-3940-5p is hsa-miR-3940-5p, miR-4725-3p is hsa-miR-4725-3p, miR-7108-5p is hsa-miR-7108-5p, miR-3656 is hsa-miR-3656, miR-6879-5p is hsa-miR-6879-5p, miR-6738-5p is hsa-miR-6738-5p, the miR-1260a hsa- is a miR-1260a, miR-4446-3p is hsa-miR-4446-3p, miR-3131 is hsa-miR-3131, miR-4463 is hsa-miR-4463, is miR-3185 is hsa-miR-3185, miR-6870-5p is hsa-miR-6870-5p, miR-6779-5p is hsa-miR-6779-5p, miR-1273g-3p is hsa-miR- a 1273g-3p, miR-8059 is hsa-miR-8059, miR-4697-5p is hsa-miR-4697-5p, miR-4674 is hsa-miR-4674, miR-4433- 3p is hsa-miR-4433-3p, miR-4257 is hsa-miR-4257, miR-1915-5p is hsa-miR-1915-5p, miR-4417 is in the hsa-miR-4417 Yes, miR-1343-5p is hsa-miR-1343-5p, miR-6781-5p is hsa-miR-6781-5p, miR-4695-5p is hsa-miR-4695-5p, miR-1237-5p is hsa-miR-1237-5p, miR-6775-5p is hsa-miR-6775-5p, miR-7845-5p is hsa-miR-7845-5p, miR- 4746-3p is hsa-miR-4746-3p, miR-7641 is hsa-miR-7641, miR-7847-3p is hsa-miR-7847-3p, the miR-6806-5p hsa- is a miR-6806-5p, miR-4467 is hsa-miR-4467, miR-4726-5p is hsa-miR-4726-5p, miR-4648 is hsa-miR-4648, miR- 6089 is hsa-miR-6089, miR-1260b is hsa-miR-1260b, miR-4532 is hsa-miR-4532, miR-5195-3p is hsa-miR-5195-3p, miR-3188 is hsa-miR-3188, miR-6848-5p is hsa-miR-6848-5p, miR-1233-5p is hsa-miR-1233-5p, the miR-6717-5p is hsa-miR-6717-5p, miR-3195 is hsa-miR-3195, miR-6757-5p is hsa-miR-6757-5p, miR-8072 is hsa-miR-8072, miR-4745-5p is hsa-miR-4745-5p, miR-6511a-5p is hsa-miR-6511a-5p, miR-6776-5p is hsa-miR-6776-5p, miR- 371a-5p is hsa-miR-371a-5p, miR-1227-5p is hsa-miR-1227-5p, miR-7150 is hsa-miR-7150, is miR-1915-3p hsa- miR-1915-3p, miR-187-5p is hsa-miR-187-5p, miR-614 is hsa-miR-614, miR-1225-5p is hsa-miR-1225-5p, miR-451a is hsa-miR-451a, miR-939-5p is hsa-miR-939-5p, miR-223-3p is hsa-miR-223-3p, the miR-125a-3p is hsa-miR-125a-3p, miR-92b-5p is hsa-miR-92b-5p, miR-22-3p is hsa-miR-22-3p, miR-6073 is hsa-miR- is 6073, miR-6845-5p is hsa-miR-6845-5p, miR-6769b-5p is hsa-miR-6769b-5p, miR-4665-3p is in hsa-miR-4665-3p Yes, miR-1913 is hsa-miR-1913, miR-1228-3p is hsa-miR-1228-3p, miR-940 is hsa-miR-940, is miR-296-3p hsa- is a miR-296-3p, miR-4690-5p is hsa-miR-4690-5p, miR-548q is hsa-miR-548q, miR-663a is hsa-miR-663a, miR- 1249 is hsa-miR-1249, miR-1202 is hsa-miR-1202, miR-7113-3p is hsa-miR-7113-3p, miR-1225-3p is hsa-miR-1225- is 3p, miR-4783-3p is hsa-miR-4783-3p, miR-4448 is hsa-miR-4448, and, miR-4534 is hsa-miR-4534, to claim 11 device described.
[13.]
Said nucleic acid, a polynucleotide shown in the following (a) -
(e): (a) SEQ ID NO: 1 ~ 125, 127 ~ 130, 132 ~ 134, and the base sequence or represented by any one of 561-578 the nucleotide u in sequence consisting of the nucleotide sequence is t polynucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, (b) SEQ ID NOs 125 and 127 ~ 130, 132 ~ 134, and a polynucleotide comprising the nucleotide sequence represented by any one of
561-578, (c) SEQ ID NOs 125 and 127 ~ 130, 132 ~ 134, and is represented by any one of 561-578 polynucleotides, a variant thereof u in the nucleotide sequence or the nucleotide sequence consisting of a nucleotide sequence complementary to the nucleotide sequence which is t, the fragment comprising the derivative, or 15 or more contiguous bases,
(d-) SEQ ID NO: 1 ~ 125, 127 ~ 130, 132 ~ 134, and, a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence shown in any 561-578 and
( e) any of the polynucleotides and a polynucleotide hybridizing under stringent conditions, the (a) ~ (d)
a polynucleotide selected from the consisting of group a device according to claim 11 or 12.
[14.]
Said device is another lung markers, miR-19b-3p, at least one or more polynucleotide specifically bindable nucleic acid selected from the group consisting of miR-1228-5p and miR-1307-3p further comprising a device according to any one of claims 11 to 13.
[15.]
miR-19b-3p is hsa-miR-19b-3p, miR-1228-5p is hsa-miR-1228-5p, and, miR-1307-3p is hsa-miR-1307-3p, device according to claim 14.
[16.]
Said nucleic acid, a polynucleotide shown in the following
(f) From (f) the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 126 and 131 and 579 comprising polynucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, polynucleotides comprising a nucleotide sequence represented by any one of (g) SEQ ID NO: 126 and 131 and
579, (h) SEQ ID NO: 126 and 131 and 579 or u in the nucleotide sequence or the nucleotide sequence represented by consists of a nucleotide sequence complementary to the nucleotide sequence is t polynucleotide, its variants, derivatives thereof, or more than 15 a fragment thereof comprising a contiguous bases,
polynucleotides comprising a nucleotide sequence complementary to the nucleotide sequence u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (i) SEQ ID NO: 126 and 131 and 579, and
(j) wherein (f) ~ any polynucleotide and a polynucleotide hybridizing under stringent conditions (i),
a polynucleotide selected from the group consisting of, according to claim 14 or 15 device.
[17.]
The device is another of lung cancer markers, miR-4271, miR-642b-3p, miR-6075, miR-6125, miR-887-3p, miR-6851-5p, miR-6763-5p, miR-3928 -3p, miR-4443, miR-3648, miR-149-3p, miR-4689, miR-4763-3p, miR-6729-5p, miR-3196, miR-8069, miR-1268a, miR-4739, miR -1268b, miR-5698, miR-6752-5p, miR-4507, miR-564, miR-4497, miR-6877-5p, miR-6087, miR-4731-5p, miR-615-5p, miR-760 , miR-6891-5p, miR-6887-5p, miR-4525, miR-1914-3p, miR-619-5p, miR-5001-5p, miR-6722-3p, miR-3621, miR-4298, miR -675-5p and further comprising at least one polynucleotide capable of specifically bound nucleic acid is selected from the group consisting of miR-4655-5p, the device according to any one of claims 11 to 16 .
[18.]
miR-4271 is hsa-miR-4271, miR-642b-3p is hsa-miR-642b-3p, miR-6075 is hsa-miR-6075, miR-6125 is in the hsa-miR-6125 Yes, miR-887-3p is hsa-miR-887-3p, miR-6851-5p is hsa-miR-6851-5p, miR-6763-5p is hsa-miR-6763-5p, miR-3928-3p is hsa-miR-3928-3p, miR-4443 is hsa-miR-4443, miR-3648 is hsa-miR-3648, miR-149-3p is hsa-miR- a 149-3p, miR-4689 is hsa-miR-4689, miR-4763-3p is hsa-miR-4763-3p, miR-6729-5p is hsa-miR-6729-5p, miR-3196 is hsa-miR-3196, miR-8069 is hsa-miR-8069, miR-1268a is hsa-miR-1268a, miR-4739 is hsa-miR-4739, miR- 1268b is hsa-miR-1268b, miR-5698 is hsa-miR-5698, miR-6752-5p is hsa-miR-6752-5p, miR-4507 is hsa-miR-4507, miR-564 is hsa-miR-564, miR-4497 is hsa-miR-4497, miR-6877-5p is hsa-miR-6877-5p, miR-6087 is in the hsa-miR-6087 Yes, miR-4731-5p is hsa-miR-4731-5p, miR-615-5p is hsa-miR-615-5p, miR-760 is hsa-miR-760, miR-6891- 5p is hsa-miR-6891-5p, miR-6887-5p is hsa-miR-6887-5p, miR-4525 is hsa-miR-4525, miR-1914-3p is hsa-miR- a 1914-3p, miR-619-5p is hsa-miR-619-5p, miR-5001-5p is hsa-miR-5001-5p, miR-6722-3p is hsa-miR-6722- is 3p, miR-3621 is hsa-miR-3621, miR-4298 is hsa-miR-4298, miR-675-5p is hsa-miR-675-5p, and, miR-4655- 5p is hsa-miR-4655-5p, device of claim 17.
[19.]
Said nucleic acid, the following (k) a polynucleotide shown in ~ (o):
(k) Poly u in the nucleotide sequence or the nucleotide sequence represented by any of SEQ ID NO: 135 ~ 174 consisting of a nucleotide sequence which is at t nucleotides, a variant thereof, a derivative thereof, or a fragment comprising 15 or more continuous
nucleotides, polynucleotides comprising a nucleotide sequence represented by any of (l) SEQ ID NO: 135 ~ 174, (m) SEQ ID NO: 135 ~ polynucleotides u in the nucleotide sequence or the nucleotide sequence represented by any one of 174 consisting of a nucleotide sequence complementary to the nucleotide sequence which is t, a variant thereof, the derivatives thereof, or 15 or more contiguous bases fragment,
a polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence that u is t in the nucleotide sequence or the nucleotide sequence represented by any one of (n) SEQ ID NO: 135-174, and
(o) the (k) any polynucleotide under stringent conditions with a polynucleotide hybridizing of ~ (n),
is a polynucleotide selected from the group consisting of, a device according to claim 17 or 18.
[20.]
It said device is a device for measuring by hybridization techniques, according to any one of claims 11 to 19 devices.
[21.]
The hybridization techniques, a nucleic acid array technology, according to claim 20 devices.
[22.]
The device comprises at least two or more nucleic acids respectively capable of specifically binding at least two or more polynucleotides selected from all lung marker according to claim 11 or 12, claims 11-21 device according to any one of.
[23.]
Using a device according to any one of claims 1 kit according to any one of 10 or claims 11 to 22 to measure the expression level of a target nucleic acid in the specimen of a subject, is the measurement and the expression level comprises assessing the in vitro, have not been affected that the subject is suffering from lung cancer, or lung cancer by using the control expression level in healthy body that is measured similarly, lung cancer method of detection.
[24.]
The subject is a human The method of claim 23.
[25.]
The sample is blood, serum or plasma Method according to claim 23 or 24.
| Section | Controller | Decision Date |
|---|---|---|
| # | Name | Date |
|---|---|---|
| 1 | 201737001450-IntimationOfGrant19-05-2023.pdf | 2023-05-19 |
| 1 | Sequence listing(PDF) [13-01-2017(online)].pdf | 2017-01-13 |
| 2 | 201737001450-PatentCertificate19-05-2023.pdf | 2023-05-19 |
| 2 | Sequence listing [13-01-2017(online)].txt | 2017-01-13 |
| 3 | Sequence listing [13-01-2017(online)].pdf | 2017-01-13 |
| 3 | 201737001450-FORM 3 [17-05-2023(online)].pdf | 2023-05-17 |
| 4 | PROOF OF RIGHT [13-01-2017(online)].pdf | 2017-01-13 |
| 4 | 201737001450-FORM 3 [29-03-2023(online)].pdf | 2023-03-29 |
| 5 | Power of Attorney [13-01-2017(online)].pdf | 2017-01-13 |
| 5 | 201737001450-Written submissions and relevant documents [01-03-2023(online)].pdf | 2023-03-01 |
| 6 | Form 5 [13-01-2017(online)].pdf | 2017-01-13 |
| 6 | 201737001450-FORM-26 [23-02-2023(online)].pdf | 2023-02-23 |
| 7 | Form 3 [13-01-2017(online)].pdf | 2017-01-13 |
| 7 | 201737001450-Correspondence to notify the Controller [17-02-2023(online)].pdf | 2023-02-17 |
| 8 | Form 20 [13-01-2017(online)].pdf | 2017-01-13 |
| 8 | 201737001450-FORM-26 [17-02-2023(online)].pdf | 2023-02-17 |
| 9 | 201737001450-US(14)-ExtendedHearingNotice-(HearingDate-24-02-2023).pdf | 2023-02-02 |
| 9 | Drawing [13-01-2017(online)].pdf | 2017-01-13 |
| 10 | 201737001450-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [30-01-2023(online)].pdf | 2023-01-30 |
| 10 | Description(Complete) [13-01-2017(online)].pdf_99.pdf | 2017-01-13 |
| 11 | 201737001450-FORM 3 [18-01-2023(online)].pdf | 2023-01-18 |
| 11 | Description(Complete) [13-01-2017(online)].pdf | 2017-01-13 |
| 12 | 201737001450-US(14)-HearingNotice-(HearingDate-02-02-2023).pdf | 2023-01-12 |
| 12 | Marked Copy [17-02-2017(online)].pdf | 2017-02-17 |
| 13 | 201737001450-FORM 3 [16-08-2022(online)].pdf | 2022-08-16 |
| 13 | Form 13 [17-02-2017(online)].pdf | 2017-02-17 |
| 14 | 201737001450-FORM 3 [12-11-2021(online)].pdf | 2021-11-12 |
| 14 | Description(Complete) [17-02-2017(online)].pdf_132.pdf | 2017-02-17 |
| 15 | 201737001450-FER.pdf | 2021-10-18 |
| 15 | Description(Complete) [17-02-2017(online)].pdf | 2017-02-17 |
| 16 | 201737001450-PETITION UNDER RULE 137 [17-06-2021(online)].pdf | 2021-06-17 |
| 16 | Information under section 8(2) [01-07-2017(online)].pdf | 2017-07-01 |
| 17 | 201737001450-FORM-26 [13-03-2018(online)].pdf | 2018-03-13 |
| 17 | 201737001450-CLAIMS [16-06-2021(online)].pdf | 2021-06-16 |
| 18 | 201737001450-CORRESPONDENCE [16-06-2021(online)].pdf | 2021-06-16 |
| 18 | 201737001450-MARKED COPIES OF AMENDEMENTS [15-06-2018(online)].pdf | 2018-06-15 |
| 19 | 201737001450-DRAWING [16-06-2021(online)].pdf | 2021-06-16 |
| 19 | 201737001450-FORM 18 [15-06-2018(online)].pdf | 2018-06-15 |
| 20 | 201737001450-AMMENDED DOCUMENTS [15-06-2018(online)].pdf | 2018-06-15 |
| 20 | 201737001450-FER_SER_REPLY [16-06-2021(online)].pdf | 2021-06-16 |
| 21 | 201737001450-Amendment Of Application Before Grant - Form 13 [15-06-2018(online)].pdf | 2018-06-15 |
| 21 | 201737001450-FORM 3 [16-06-2021(online)].pdf | 2021-06-16 |
| 22 | 201737001450-FORM 3 [18-04-2020(online)].pdf | 2020-04-18 |
| 22 | 201737001450-FORM-26 [16-06-2021(online)].pdf | 2021-06-16 |
| 23 | 201737001450-Certified Copy of Priority Document [26-12-2020(online)].pdf | 2020-12-26 |
| 23 | 201737001450-OTHERS [16-06-2021(online)].pdf | 2021-06-16 |
| 24 | 201737001450-FORM 4(ii) [13-03-2021(online)].pdf | 2021-03-13 |
| 25 | 201737001450-OTHERS [16-06-2021(online)].pdf | 2021-06-16 |
| 25 | 201737001450-Certified Copy of Priority Document [26-12-2020(online)].pdf | 2020-12-26 |
| 26 | 201737001450-FORM 3 [18-04-2020(online)].pdf | 2020-04-18 |
| 26 | 201737001450-FORM-26 [16-06-2021(online)].pdf | 2021-06-16 |
| 27 | 201737001450-Amendment Of Application Before Grant - Form 13 [15-06-2018(online)].pdf | 2018-06-15 |
| 27 | 201737001450-FORM 3 [16-06-2021(online)].pdf | 2021-06-16 |
| 28 | 201737001450-AMMENDED DOCUMENTS [15-06-2018(online)].pdf | 2018-06-15 |
| 28 | 201737001450-FER_SER_REPLY [16-06-2021(online)].pdf | 2021-06-16 |
| 29 | 201737001450-DRAWING [16-06-2021(online)].pdf | 2021-06-16 |
| 29 | 201737001450-FORM 18 [15-06-2018(online)].pdf | 2018-06-15 |
| 30 | 201737001450-CORRESPONDENCE [16-06-2021(online)].pdf | 2021-06-16 |
| 30 | 201737001450-MARKED COPIES OF AMENDEMENTS [15-06-2018(online)].pdf | 2018-06-15 |
| 31 | 201737001450-CLAIMS [16-06-2021(online)].pdf | 2021-06-16 |
| 31 | 201737001450-FORM-26 [13-03-2018(online)].pdf | 2018-03-13 |
| 32 | 201737001450-PETITION UNDER RULE 137 [17-06-2021(online)].pdf | 2021-06-17 |
| 32 | Information under section 8(2) [01-07-2017(online)].pdf | 2017-07-01 |
| 33 | 201737001450-FER.pdf | 2021-10-18 |
| 33 | Description(Complete) [17-02-2017(online)].pdf | 2017-02-17 |
| 34 | 201737001450-FORM 3 [12-11-2021(online)].pdf | 2021-11-12 |
| 34 | Description(Complete) [17-02-2017(online)].pdf_132.pdf | 2017-02-17 |
| 35 | 201737001450-FORM 3 [16-08-2022(online)].pdf | 2022-08-16 |
| 35 | Form 13 [17-02-2017(online)].pdf | 2017-02-17 |
| 36 | Marked Copy [17-02-2017(online)].pdf | 2017-02-17 |
| 36 | 201737001450-US(14)-HearingNotice-(HearingDate-02-02-2023).pdf | 2023-01-12 |
| 37 | 201737001450-FORM 3 [18-01-2023(online)].pdf | 2023-01-18 |
| 37 | Description(Complete) [13-01-2017(online)].pdf | 2017-01-13 |
| 38 | 201737001450-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [30-01-2023(online)].pdf | 2023-01-30 |
| 38 | Description(Complete) [13-01-2017(online)].pdf_99.pdf | 2017-01-13 |
| 39 | 201737001450-US(14)-ExtendedHearingNotice-(HearingDate-24-02-2023).pdf | 2023-02-02 |
| 39 | Drawing [13-01-2017(online)].pdf | 2017-01-13 |
| 40 | 201737001450-FORM-26 [17-02-2023(online)].pdf | 2023-02-17 |
| 40 | Form 20 [13-01-2017(online)].pdf | 2017-01-13 |
| 41 | 201737001450-Correspondence to notify the Controller [17-02-2023(online)].pdf | 2023-02-17 |
| 41 | Form 3 [13-01-2017(online)].pdf | 2017-01-13 |
| 42 | Form 5 [13-01-2017(online)].pdf | 2017-01-13 |
| 42 | 201737001450-FORM-26 [23-02-2023(online)].pdf | 2023-02-23 |
| 43 | Power of Attorney [13-01-2017(online)].pdf | 2017-01-13 |
| 43 | 201737001450-Written submissions and relevant documents [01-03-2023(online)].pdf | 2023-03-01 |
| 44 | PROOF OF RIGHT [13-01-2017(online)].pdf | 2017-01-13 |
| 44 | 201737001450-FORM 3 [29-03-2023(online)].pdf | 2023-03-29 |
| 45 | 201737001450-FORM 3 [17-05-2023(online)].pdf | 2023-05-17 |
| 46 | Sequence listing [13-01-2017(online)].txt | 2017-01-13 |
| 46 | 201737001450-PatentCertificate19-05-2023.pdf | 2023-05-19 |
| 47 | Sequence listing(PDF) [13-01-2017(online)].pdf | 2017-01-13 |
| 47 | 201737001450-IntimationOfGrant19-05-2023.pdf | 2023-05-19 |
| 1 | 201737001450seq1E_13-09-2020.pdf |
| 1 | 201737001450tpoE_13-09-2020.pdf |
| 2 | 201737001450seq1E_13-09-2020.pdf |
| 2 | 201737001450tpoE_13-09-2020.pdf |