Detection Kit or Device and Detection Method for Early Pancreatic Cancer or Pancreatic Cancer Precursors
A non-invasive kit and device using specific miRNA-binding nucleic acids effectively detects early pancreatic cancer and precursor lesions, addressing the limitations of current methods by enhancing sensitivity and specificity.
Patent Information
- Application Number
- JP2023185506
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2016-03-31
- Filing Date
- 2023-10-30
- Publication Date
- 2025-06-25
- Estimated Expiration
- 2037-03-31
Smart Images

Figure 0007698275000059 
Figure 0007698275000060 
Figure 0007698275000061
Abstract
Description
Technical Field
[0001] The present invention relates to a kit or device for detecting early pancreatic cancer or a pancreatic cancer precursor lesion, which contains a nucleic acid capable of specifically binding to a specific miRNA and is used for detecting the presence or absence of early pancreatic cancer or pancreatic cancer precursor lesion in a subject, and a method for detecting early pancreatic cancer or a pancreatic cancer precursor lesion, which includes measuring the expression level of the miRNA using the nucleic acid.
Background Art
[0002] The pancreas is an exocrine gland that secretes pancreatic juice, a digestive fluid, and sends it into the digestive tract through the pancreatic duct. It also functions as an endocrine gland that secretes hormones such as insulin and glucagon into the blood.
[0003] Because the pancreas is surrounded by many organs such as the stomach, duodenum, small intestine, liver, and gallbladder, it is not only difficult to detect cancer at an early stage, but also has properties such as no self-awareness symptoms, very rapid progression, and metastasis to other organs. It is a cancer with extremely poor prognosis compared to other cancers. According to the statistics of cancer mortality by site in Japan in 2011 disclosed by the Cancer Control Information Center of the National Cancer Center, National Institutes of Biomedical Innovation, Health and Nutrition (Tokyo, Japan), the number of deaths from pancreatic cancer reached 28,829. The 5-year relative survival rate by site from 2003 to 2005 was the lowest for pancreatic cancer, 7.1% for men and 6.9% for women.
[0004] As described in Non-Patent Document 1, the basic treatment for pancreatic cancer is surgery, systemic chemotherapy, radiotherapy, or a combination thereof, depending on the degree of progression. Surgery has been performed on 15 - 20% of pancreatic cancer patients, who are considered curable, but most patients who did not undergo surgery are thought to have progressed locally or metastasized.
[0005] The progression of pancreatic cancer by UICC (Union International Against Cancer) is classified into stage 0, IA, IB, IIA, IIB, III, IVa, and IVb. Stages I - III account for more than half of the 5-year survival cases, and the progression at the time of diagnosis is more than 70% in Stages IVa and IVb. As described in Non-Patent Document 1, the 5-year survival rate of pancreatic cancer is 45.8% for stage IA, 36.3% for stage IB, 29.4% for stage IIA, 10.6% for stage IIB, 5.9% for stage III, and 4.0% for stage IV. Since the prognosis of stages III and IV is extremely poor, it is necessary to detect and treat pancreatic cancer at an early stage.
[0006] As described in Non-Patent Document 2, in the diagnosis of pancreatic cancer, abdominal ultrasonography is a simple and minimally invasive examination and is very useful in outpatient clinics and mass screenings. However, it is often difficult to detect pancreatic cancers with a small tumor diameter or lesions in the tail of the pancreas. The detection rate of pancreatic images by abdominal ultrasonography in a normal health check is about 1%, and the detection rate of pancreatic cancer is as low as about 0.06% or less. Also, as tumor markers for the detection of pancreatic cancer, for example, as carbohydrate antigens, CA19-9, Span-1, CA50, CA242, Dupan-2, TAG-72, urinary fucose, etc., and as antigens other than carbohydrates, CEA, POA, TPS, etc. are known. As for the usage of these tumor markers, cancer is suspected when their blood concentration is higher or lower than a previously set reference value. For example, as described in Non-Patent Document 3, the reference value of CEA is set at 5 ng / mL, and the reference value of CA19-9 is set at 37 U / mL. When values higher than these are shown, cancer including pancreatic cancer is suspected. However, most evaluations of tumor markers are studies on advanced pancreatic cancer, and abnormal values are often not shown in early pancreatic cancer. Also, even if tumor markers and abdominal ultrasonography are performed in mass screenings, the detection rate of pancreatic cancer is low, and the implementation of these mass screenings for the discovery of pancreatic cancer has problems in terms of cost-effectiveness.
[0007] On the one hand, cystic diseases occurring in the pancreas are known to progress to invasive cancer by malignant transformation and can be regarded as pancreatic cancer precursor lesions. As described in Non-Patent Document 4, the malignancy of cystic diseases is evaluated by cyst diameter, wall thickening, main pancreatic duct diameter, intramural nodules, main pancreatic duct stenosis, lymph node enlargement, and cystic lesions, etc. In the case of intraductal papillary mucinous neoplasm, which is a type of cystic disease, the prognosis is poor with a malignancy rate of 40.4% and an invasive cancer rate of 30.8%. Therefore, even when the malignancy at the time of discovery is low, follow-up observation or resection is recommended.
[0008] Although still in the research stage, as shown in Patent Documents 1 to 5 and Non-Patent Document 5, there are reports of discriminating pancreatic cancer by combining the expression levels of microRNA (miRNA) in biological samples including blood, or the expression levels of miRNA and the expression levels of other protein markers.
[0009] Patent Document 1 shows a method for detecting pancreatic cancer by combining hsa-miR-125a-3p, hsa-miR-204-3p, hsa-miR-3648 in blood with several other miRNAs.
[0010] Patent Document 2 shows a method for detecting pancreatic cancer by combining miRNAs such as hsa-miR-1908-5p, hsa-miR-6729-5p, hsa-miR-5195-3p in blood.
[0011] Patent Document 3 shows a method for detecting pancreatic cancer by combining miR-23a-3p in blood with several other dozens of miRNAs.
[0012] Patent Document 4 lists hsa-miR-1268a, hsa-miR-939-5p, and hsa-miR-642b-3p as miRNAs with increased expression levels in the blood of pancreatic cancer patients compared to healthy individuals, and shows methods for detecting pancreatic cancer by combining them with several other dozens of miRNAs, as well as methods for evaluating the risk of developing pancreatic cancer.
[0013] Patent Document 5 discloses a method for detecting pancreatic cancer and pancreatic cancer precursor lesions by combining hsa-miR-296-5p in blood with several other miRNAs, and a method for evaluating the risk of developing pancreatic cancer.
[0014] Non-Patent Document 5 lists hsa-miR-638, hsa-miR-3196, hsa-miR-1225-3p, etc. as miRNAs whose expression levels increase in the blood of pancreatic cancer patients compared to healthy individuals, and discloses a method for detecting pancreatic cancer by combining several of these miRNAs.
Prior Art Documents
Patent Documents
[0015]
Patent Document 1
Patent Document 2
Patent Document 3
Patent Document 4
Patent Document 5
Non-Patent Documents
[0016]
Non-Patent Document 1
Non-Patent Document 2
Non-Patent Document 3
Non-Patent Document 4
Non-Patent Document 5
Summary of the Invention
Problems to be Solved by the Invention
[0017] The problem of the present invention is to find a novel early pancreatic cancer or pancreatic cancer precursor lesion tumor marker, and to provide a method capable of effectively detecting early pancreatic cancer or pancreatic cancer precursor lesions using a nucleic acid that can specifically bind to the marker. As described in Non-Patent Document 2, tumor markers for pancreatic cancer detection include, for example, CA19-9, Span-1, CA50, CA242, Dupan-2, TAG-72, urinary fucose, etc. as carbohydrate antigens, or CEA, POA, TPS, etc. as antigens other than carbohydrates. The pancreatic cancer detection sensitivity of these tumor markers is 70-80% for CA19-9, 70-80% for Span-1, 50-60% for Dupan-2, 30-60% for CEA, and 60% for CA50. Also, the specificity is not very high, and the false positive rate is as high as 20-30%. Therefore, there is a possibility of misdetecting other cancers and / or benign tumors and / or benign diseases of the pancreas and / or surrounding organs of the pancreas. In addition, the detection sensitivity of early pancreatic cancer is generally low. For pancreatic cancers less than 2 cm, the positive rate of CA19-9 is only 52%, which is less than half. Therefore, it is not useful for the detection of early pancreatic cancer. In addition, tumor markers based on carbohydrate antigens are inappropriate tests for some subjects because the antigen is not produced in Lewis blood type negative cases, showing false negatives. Also, the detection rates of intraductal papillary mucinous neoplasms, which are pancreatic cancer precursor lesions, by MRI and CT are 19.9% and 1.2-2.6% respectively, which are not sufficient. The use of tumor markers for the detection of pancreatic cancer precursor lesions is not recommended.
[0018] Although still in the research stage, there are reports of using the expression levels of microRNAs (miRNAs) in biological samples such as blood to discriminate pancreatic cancer, but none of them have been put into practical use as a method for detecting early-stage pancreatic cancer or pancreatic cancer precursor lesions.
[0019] Patent Document 1 shows a method for detecting pancreatic cancer by combining miR-125a-3p, miR-204-3p, miR-3648 in blood with several other miRNAs. However, only healthy individuals are used as the negative control group for pancreatic cancer, and there is no description of cancers or benign diseases of organs other than the pancreas, nor is there a description of a specific method for detecting pancreatic cancer precursor lesions using blood.
[0020] Patent Document 2 shows a method for detecting pancreatic cancer by combining miRNAs such as hsa-miR-1908-5p, hsa-miR-6729-5p, hsa-miR-5195-3p in blood. However, only a few specimens of early-stage pancreatic cancer patients are included, and there is no description of the detection performance such as the specific accuracy, sensitivity, and specificity for early-stage pancreatic cancer, nor is there a description of a specific method for detecting pancreatic cancer precursor lesions using blood.
[0021] Patent Document 3 shows a method for detecting pancreatic cancer by combining hsa-miR-23a-3p in blood with several other dozens of miRNAs. However, there is no description of the detection performance such as the specific accuracy, sensitivity, and specificity for early-stage pancreatic cancer, and there is no description of cancers other than those in the upper gastrointestinal tract around the pancreas as the negative control group for pancreatic cancer, nor is there a description of a method for detecting pancreatic cancer precursor lesions.
[0022] Patent Document 4 shows a method for detecting pancreatic cancer and pancreatic cancer precursor lesions by combining hsa-miR-1268a, hsa-miR-939-5p, and hsa-miR-642b-3p with several other dozens of miRNAs. However, there is no description of the detection performance such as the specific accuracy, sensitivity, and specificity for pancreatic cancer, nor is there a description of cancers of organs other than the pancreas as the negative control group for pancreatic cancer.
[0023] Patent Document 5 discloses a method for detecting pancreatic cancer and pancreatic cancer precursor lesions by combining hsa-miR-296-5p in blood with dozens of other miRNAs. However, there is no description of the detection performance such as the specific accuracy, sensitivity, and specificity for early pancreatic cancer. Cancer and benign diseases of organs other than the pancreas are not measured as the negative control group for pancreatic cancer precursor lesions, and the specific specificity is not described either.
[0024] Non-Patent Document 5 lists hsa-miR-638, hsa-miR-3196, hsa-miR-1225-3p, etc. as miRNAs with increased expression levels in the blood of pancreatic cancer patients compared to healthy subjects, and shows a method for detecting pancreatic cancer by combining several of these miRNAs. However, there is no description of cancer in organs other than the pancreas as the negative control group for pancreatic cancer.
[0025] Thus, in the detection of early pancreatic cancer or pancreatic cancer precursor lesions, the performance of existing tumor markers is low, or for markers in the research stage, the performance and detection methods are not specifically shown. Therefore, when using these, there may be a waste of additional examinations due to misdetecting healthy subjects as early pancreatic cancer or pancreatic cancer precursor lesion patients, or a loss of treatment opportunities due to overlooking early pancreatic cancer or pancreatic cancer precursor lesion patients. In addition, measuring dozens to hundreds of miRNAs increases the examination cost, so it is difficult to use in large-scale screenings such as health check-ups. Also, collecting pancreatic tissue to measure tumor markers is highly invasive to patients and not preferable. Therefore, there is a need for a highly accurate early pancreatic cancer or pancreatic cancer precursor lesion marker that can detect from blood, which can be collected with low invasiveness, and can correctly distinguish early pancreatic cancer or pancreatic cancer precursor lesion patients from early pancreatic cancer or pancreatic cancer precursor lesion patients and healthy subjects from healthy subjects. In particular, since resection by early detection is the only radical treatment for pancreatic cancer, a highly sensitive early pancreatic cancer or pancreatic cancer precursor lesion marker is eagerly awaited.
Means for Solving the Problems
[0026] As a result of intensive studies to solve the above problems, the present inventors have found several genes that can be used as detection markers for early pancreatic cancer or pancreatic cancer precursor lesions that can be obtained with minimal invasion, and have found that early pancreatic cancer or pancreatic cancer precursor lesions can be significantly detected by using a nucleic acid that can specifically bind thereto, thus completing the present invention.
[0027] <Summary of the Invention> That is, the present invention has the following features. (1) miR-6784-5p, miR-1181, miR-671-5p, miR-6857-5p, miR-4276, miR-1914-3p, miR-149-3p, miR-937-5p, miR-4675, miR-6795-5p, miR-4731-5p, miR-5090, miR-3620-5p, miR-1343-5p, miR-6717-5p, miR-6825-5p, miR-6738-5p, miR-6769a-5p, miR-4728-5p, miR-652-5p, miR-4257, miR-6785-5p, miR-7110-5p, miR-6887-5p, miR-887-3p, miR-1228-5p, miR-5572, miR-6782-5p, miR-4298, miR-6786-5p, miR-5010-5p, miR-6087, miR-6765-5p, miR-6732-5p, miR-6787-5p, miR-6737-5p, miR-128-2-5p, miR-4270, miR-6861-5p, miR-6756-5p, miR-1229-5p, miR-6891-5p, miR-6848-5p, miR-1237-5p, miR-30c-1-3p, miR-1233-5p, miR-211-3p, miR-4758-5p, miR-614, miR-6746-5p, miR-1915-5p, miR-4688, miR-3917, miR-5787, miR-4632-5p, miR-6126, miR-135a-3p, miR-8063, miR-5698, miR-6089, miR-498, miR-296-3p, miR-4419b, miR-6802-5p, miR-6829-5p, miR-6803-5p, miR-1199-5p, miR-6840-3p, miR-6752-5p, miR-6798-5p, miR-6131, miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920, miR-23b-3p, miR-4448, miR-2110, miR-4706, miR-7845-5p, miR-6808-5p, miR-4447, miR-6869-5p, miR-6794-5p, miR-6511a-5p, miR-6824-5p, miR-6766-3p, miR-6511a-5p, which are markers for early pancreatic cancer or pancreatic cancer precursor lesionsA kit for detecting early pancreatic cancer or pancreatic cancer precursor lesions, comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-6749-5p.
[0028] (2) miR-6784-5p is hsa-miR-6784-5p, miR-1181 is hsa-miR-1181, miR-671-5p is hsa-miR-671-5p, miR-6857-5p is hsa-miR-6857-5p, miR-4276 is hsa-miR-4276, miR-1914-3p is hsa-miR-1914-3p, miR-149-3p is hsa-miR-149-3p, miR-937-5p is hsa-miR-937-5p, miR-4675 is hsa-miR-4675, miR-6795-5p is hsa-miR-6795-5p, miR-4731-5p is hsa-miR-4731-5p, miR-5090 is hsa-miR-5090, miR-3620-5p is hsa-miR-3620-5p, miR-1343-5p is hsa-miR-1343-5p, miR-6717-5p is hsa-miR-6717-5p, miR-6825-5p is hsa-miR-6825-5p, miR-6738-5p is hsa-miR-6738-5p, miR-6769a-5p is hsa-miR-6769a-5p, miR-4728-5p is hsa-miR-4728-5p, miR-652-5p is hsa-miR-652-5p, miR-4257 is hsa-miR-4257, miR-6785-5p is hsa-miR-6785-5p, miR-7110-5p is hsa-miR-7110-5p, miR-6887-5p is hsa-miR-6887-5p, miR-887-3p is hsa-miR-887-3p, miR-1228-5p is hsa-miR-1228-5p, miR-5572 is hsa-miR-5572, miR-6782-5p is hsa-miR-6782-5p, miR-4298 is hsa-miR-4298, miR-6786-5p is hsa-miR-6786-5p, miR-5010-5p is hsa-miR-5010-5p, miR-6087 is hsa-miR-6087, miR-6765-5p is hsa-miR-6765-5p, miR-6732-5p is hsa-miR-6732-5p,miR-6787-5p is hsa-miR-6787-5p, miR-6737-5p is hsa-miR-6737-5p, miR-128-2-5p is hsa-miR-128-2-5p, miR-4270 is hsa-miR-4270, miR-6861-5p is hsa-miR-6861-5p, miR-6756-5p is hsa-miR-6756-5p, miR-1229-5p is hsa-miR-1229-5p, miR-6891-5p is hsa-miR-6891-5p, miR-6848-5p is hsa-miR-6848-5p, miR-1237-5p is hsa-miR-1237-5p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-1233-5p is hsa-miR-1233-5p, miR-211-3p is hsa-miR-211-3p, miR-4758-5p is hsa-miR-4758-5p, miR-614 is hsa-miR-614, miR-6746-5p is hsa-miR-6746-5p, miR-1915-5p is hsa-miR-1915-5p, miR-4688 is hsa-miR-4688, miR-3917 is hsa-miR-3917, miR-5787 is hsa-miR-5787, miR-4632-5p is hsa-miR-4632-5p, miR-6126 is hsa-miR-6126, miR-135a-3p is hsa-miR-135a-3p, miR-8063 is hsa-miR-8063, miR-5698 is hsa-miR-5698, miR-6089 is hsa-miR-6089, miR-498 is hsa-miR-498, miR-296-3p is hsa-miR-296-3p, miR-4419b is hsa-miR-4419b, miR-6802-5p is hsa-miR-6802-5p, miR-6829-5p is hsa-miR-6829-5p, miR-6803-5p is hsa-miR-6803-5p, miR-1199-5p is hsa-miR-1199-5p, miR-6840-3p is hsa-miR-6840-3p,miR-6752-5p is hsa-miR-6752-5p, miR-6798-5p is hsa-miR-6798-5p, miR-6131 is hsa-miR-6131, miR-4667-5p is hsa-miR-4667-5p, miR-6510-5p is hsa-miR-6510-5p, miR-4690-5p is hsa-miR-4690-5p, miR-920 is hsa-miR-920, miR-23b-3p is hsa-miR-23b-3p, miR-4448 is hsa-miR-4448, miR-2110 is hsa-miR-2110, miR-4706 is hsa-miR-4706, miR-7845-5p is hsa-miR-7845-5p, miR-6808-5p is hsa-miR-6808-5p, miR-4447 is hsa-miR-4447, miR-6869-5p is hsa-miR-6869-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6511a-5p is hsa-miR-6511a-5p, miR-6824-5p is hsa-miR-6824-5p, miR-6766-3p is hsa-miR-6766-3p, miR-6511a-5p is hsa-miR-6511a-5p, miR-6749-5p is hsa-miR-6749-5p, the kit according to (1).
[0029] (3) The nucleic acid is a polynucleotide represented by any one of the following (a) to (e): (a) A polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (b) A polynucleotide containing a base sequence represented by any one of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, (c) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, or a base sequence complementary to a base sequence in which u is t in the said base sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (d) A polynucleotide containing a base sequence represented by any of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, or a base sequence complementary to a base sequence in which u is t in the said base sequence, and (e) A polynucleotide that hybridizes with any of the polynucleotides of (a) to (d) above under stringent conditions, The kit according to (1) or (2), which is a polynucleotide selected from the group consisting of.
[0030] (4) The kit is miR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125, miR-3178, miR-3196, miR-8069, miR-4723-5p, miR-4746-3p, miR-4689, miR-6816-5p, miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p, miR-6875-5p, miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p, miR-4695-5p, miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p, miR-3185, miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p, miR-1343-3p, miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p, miR-5100, miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718, miR-6780b-5p, miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p, miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a, miR-6791-5p, miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449, miR-4707-3p, miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p, miR-204-3p, miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p, miR-675-5p, miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p, miR-3162-5p, miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p, miR-7113-3p, miR-6850-5p, which is another early pancreatic cancer or pancreatic cancer precursor lesion marker.At least one polynucleotide selected from the group consisting of miR-6799-5p, miR-6768-5p, miR-92b-5p, miR-3679-5p, miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513, miR-6781-5p, miR-4649-5p, miR-6775-5p, miR-4651, miR-3195, miR-6726-5p, miR-6872-3p, miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975, miR-6821-5p, miR-4534, miR-619-5p, miR-7107-5p, miR-1228-3p, miR-6774-5p, miR-6805-5p, miR-23a-3p, miR-4665-5p, miR-4505, miR-4638-5p, miR-24-3p, miR-3135b, miR-4745-5p, miR-128-1-5p, miR-4476, miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141, miR-3188, miR-4281, miR-5196-5p, miR-6880-5p, miR-3960, miR-3648, miR-6721-5p, miR-4492, miR-744-5p, miR-7704, miR-4749-5p, miR-762, miR-6836-3p, miR-6727-5p, miR-4739, miR-7977, miR-4484, miR-6515-3p, miR-373-5p, miR-4258, miR-4674, miR-3180, miR-6076, miR-1238-5p, miR-4463, miR-4486, miR-4730, miR-4286, and miR-4739, and a kit according to any one of (1)-(3), further comprising a nucleic acid capable of specifically binding to the polynucleotide.
[0031] (5) miR-1908-5p is hsa-miR-1908-5p, miR-6729-5p is hsa-miR-6729-5p, miR-5195-3p is hsa-miR-5195-3p, miR-638 is hsa-miR-638, miR-6125 is hsa-miR-6125, miR-3178 is hsa-miR-3178, miR-3196 is hsa-miR-3196, miR-8069 is hsa-miR-8069, miR-4723-5p is hsa-miR-4723-5p, miR-4746-3p is hsa-miR-4746-3p, miR-4689 is hsa-miR-4689, miR-6816-5p is hsa-miR-6816-5p, miR-6757-5p is hsa-miR-6757-5p, miR-7109-5p is hsa-miR-7109-5p, miR-6724-5p is hsa-miR-6724-5p, miR-1225-3p is hsa-miR-1225-3p, miR-6875-5p is hsa-miR-6875-5p, miR-7108-5p is hsa-miR-7108-5p, miR-4508 is hsa-miR-4508, miR-6085 is hsa-miR-6085, miR-6779-5p is hsa-miR-6779-5p, miR-642a-3p is hsa-miR-642a-3p, miR-4695-5p is hsa-miR-4695-5p, miR-7847-3p is hsa-miR-7847-3p, miR-3197 is hsa-miR-3197, miR-6769b-5p is hsa-miR-6769b-5p, miR-7641 is hsa-miR-7641, miR-187-5p is hsa-miR-187-5p, miR-3185 is hsa-miR-3185, miR-2861 is hsa-miR-2861, miR-3940-5p is hsa-miR-3940-5p, miR-1203 is hsa-miR-1203, miR-615-5p is hsa-miR-615-5p, miR-4787-5p is hsa-miR-4787-5p,miR-1343-3p is hsa-miR-1343-3p, miR-6813-5p is hsa-miR-6813-5p, miR-1225-5p is hsa-miR-1225-5p, miR-602 is hsa-miR-602, miR-4488 is hsa-miR-4488, miR-125a-3p is hsa-miR-125a-3p, miR-5100 is hsa-miR-5100, miR-4294 is hsa-miR-4294, miR-1231 is hsa-miR-1231, miR-6765-3p is hsa-miR-6765-3p, miR-4442 is hsa-miR-4442, miR-718 is hsa-miR-718, miR-6780b-5p is hsa-miR-6780b-5p, miR-6090 is hsa-miR-6090, miR-6845-5p is hsa-miR-6845-5p, miR-4741 is hsa-miR-4741, miR-4467 is hsa-miR-4467, miR-4707-5p is hsa-miR-4707-5p, miR-4271 is hsa-miR-4271, miR-4673 is hsa-miR-4673, miR-3184-5p is hsa-miR-3184-5p, miR-1469 is hsa-miR-1469, miR-4640-5p is hsa-miR-4640-5p, miR-663a is hsa-miR-663a, miR-6791-5p is hsa-miR-6791-5p, miR-6826-5p is hsa-miR-6826-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-1915-3p is hsa-miR-1915-3p, miR-4417 is hsa-miR-4417, miR-4449 is hsa-miR-4449, miR-4707-3p is hsa-miR-4707-3p, miR-3180-3p is hsa-miR-3180-3p, miR-5585-3p is hsa-miR-5585-3p, miR-1268a is hsa-miR-1268a, miR-8072 is hsa-miR-8072,miR-296-5p is hsa-miR-296-5p, miR-204-3p is hsa-miR-204-3p, miR-4454 is hsa-miR-4454, miR-6722-3p is hsa-miR-6722-3p, miR-1290 is hsa-miR-1290, miR-3622a-5p is hsa-miR-3622a-5p, miR-939-5p is hsa-miR-939-5p, miR-675-5p is hsa-miR-675-5p, miR-3131 is hsa-miR-3131, miR-4648 is hsa-miR-4648, miR-1268b is hsa-miR-1268b, miR-6741-5p is hsa-miR-6741-5p, miR-6893-5p is hsa-miR-6893-5p, miR-3162-5p is hsa-miR-3162-5p, miR-642b-3p is hsa-miR-642b-3p, miR-4734 is hsa-miR-4734, miR-150-3p is hsa-miR-150-3p, miR-8089 is hsa-miR-8089, miR-6805-3p is hsa-miR-6805-3p, miR-7113-3p is hsa-miR-7113-3p, miR-6850-5p is hsa-miR-6850-5p, miR-6799-5p is hsa-miR-6799-5p, miR-6768-5p is hsa-miR-6768-5p, miR-92b-5p is hsa-miR-92b-5p, miR-3679-5p is hsa-miR-3679-5p, miR-4792 is hsa-miR-4792, miR-3656 is hsa-miR-3656, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-4466 is hsa-miR-4466, miR-4513 is hsa-miR-4513, miR-6781-5p is hsa-miR-6781-5p, miR-4649-5p is hsa-miR-4649-5p, miR-6775-5p is hsa-miR-6775-5p, miR-4651 is hsa-miR-4651, miR-3195 is hsa-miR-3195,miR-6726-5p is hsa-miR-6726-5p, miR-6872-3p is hsa-miR-6872-3p, miR-371a-5p is hsa-miR-371a-5p, miR-6777-5p is hsa-miR-6777-5p, miR-6789-5p is hsa-miR-6789-5p, miR-7975 is hsa-miR-7975, miR-6821-5p is hsa-miR-6821-5p, miR-4534 is hsa-miR-4534, miR-619-5p is hsa-miR-619-5p, miR-7107-5p is hsa-miR-7107-5p, miR-1228-3p is hsa-miR-1228-3p, miR-6774-5p is hsa-miR-6774-5p, miR-6805-5p is hsa-miR-6805-5p, miR-23a-3p is hsa-miR-23a-3p, miR-4665-5p is hsa-miR-4665-5p, miR-4505 is hsa-miR-4505, miR-4638-5p is hsa-miR-4638-5p, miR-24-3p is hsa-miR-24-3p, miR-3135b is hsa-miR-3135b, miR-4745-5p is hsa-miR-4745-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-4476 is hsa-miR-4476, miR-4687-3p is hsa-miR-4687-3p, miR-3665 is hsa-miR-3665, miR-6806-5p is hsa-miR-6806-5p, miR-3937 is hsa-miR-3937, miR-711 is hsa-miR-711, miR-3141 is hsa-miR-3141, miR-3188 is hsa-miR-3188, miR-4281 is hsa-miR-4281, miR-5196-5p is hsa-miR-5196-5p, miR-6880-5p is hsa-miR-6880-5p, miR-3960 is hsa-miR-3960, miR-3648 is hsa-miR-3648, miR-6721-5p is hsa-miR-6721-5p,miR-4492 is hsa-miR-4492, miR-744-5p is hsa-miR-744-5p, miR-7704 is hsa-miR-7704, miR-4749-5p is hsa-miR-4749-5p, miR-762 is hsa-miR-762, miR-6836-3p is hsa-miR-6836-3p, miR-6727-5p is hsa-miR-6727-5p, miR-4739 is hsa-miR-4739, miR-7977 is hsa-miR-7977, miR-4484 is hsa-miR-4484, miR-6515-3p is hsa-miR-6515-3p, miR-373-5p is hsa-miR-373-5p, miR-4258 is hsa-miR-4258, miR-4674 is hsa-miR-4674, miR-3180 is hsa-miR-3180, miR-6076 is hsa-miR-6076, miR-1238-5p is hsa-miR-1238-5p, miR-4463 is hsa-miR-4463, miR-4486 is hsa-miR-4486, miR-4730 is hsa-miR-4730, miR-4286 is hsa-miR-4286, miR-4739 is hsa-miR-4739, the kit according to (4).
[0032] (6) The nucleic acid is a polynucleotide represented by any one of the following (f) to (j): (f) A polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249, or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases (g) A polynucleotide containing a base sequence represented by any one of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 (h) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a base sequence complementary to a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (i) A polynucleotide containing a base sequence represented by any of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a base sequence complementary to a base sequence in which u is t in the base sequence, and (j) A polynucleotide that hybridizes with any of the polynucleotides of (f) to (i) under stringent conditions, The kit according to (4) or (5), which is a polynucleotide selected from the group consisting of
[0033] (7) miR-6784-5p, miR-1181, miR-671-5p, miR-6857-5p, miR-4276, miR-1914-3p, miR-149-3p, miR-937-5p, miR-4675, miR-6795-5p, miR-4731-5p, miR-5090, miR-3620-5p, miR-1343-5p, miR-6717-5p, miR-6825-5p, miR-6738-5p, miR-6769a-5p, miR-4728-5p, miR-652-5p, miR-4257, miR-6785-5p, miR-7110-5p, miR-6887-5p, miR-887-3p, miR-1228-5p, miR-5572, miR-6782-5p, miR-4298, miR-6786-5p, miR-5010-5p, miR-6087, miR-6765-5p, miR-6732-5p, miR-6787-5p, miR-6737-5p, miR-128-2-5p, miR-4270, miR-6861-5p, miR-6756-5p, miR-1229-5p, miR-6891-5p, miR-6848-5p, miR-1237-5p, miR-30c-1-3p, miR-1233-5p, miR-211-3p, miR-4758-5p, miR-614, miR-6746-5p, miR-1915-5p, miR-4688, miR-3917, miR-5787, miR-4632-5p, miR-6126, miR-135a-3p, miR-8063, miR-5698, miR-6089, miR-498, miR-296-3p, miR-4419b, miR-6802-5p, miR-6829-5p, miR-6803-5p, miR-1199-5p, miR-6840-3p, miR-6752-5p, miR-6798-5p, miR-6131, miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920, miR-23b-3p, miR-4448, miR-2110, miR-4706, miR-7845-5p, miR-6808-5p, miR-4447, miR-6869-5p, miR-6794-5p, miR-6511a-5p, miR-6824-5p, miR-6766-3p, miR-6511a-5p, which are markers for early pancreatic cancer or pancreatic cancer precursor lesionsA device for detecting early pancreatic cancer or pancreatic cancer precursor lesions, comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from miR-6749-5p.
[0034] (8) miR-6784-5p is hsa-miR-6784-5p, miR-1181 is hsa-miR-1181, miR-671-5p is hsa-miR-671-5p, miR-6857-5p is hsa-miR-6857-5p, miR-4276 is hsa-miR-4276, miR-1914-3p is hsa-miR-1914-3p, miR-149-3p is hsa-miR-149-3p, miR-937-5p is hsa-miR-937-5p, miR-4675 is hsa-miR-4675, miR-6795-5p is hsa-miR-6795-5p, miR-4731-5p is hsa-miR-4731-5p, miR-5090 is hsa-miR-5090, miR-3620-5p is hsa-miR-3620-5p, miR-1343-5p is hsa-miR-1343-5p, miR-6717-5p is hsa-miR-6717-5p, miR-6825-5p is hsa-miR-6825-5p, miR-6738-5p is hsa-miR-6738-5p, miR-6769a-5p is hsa-miR-6769a-5p, miR-4728-5p is hsa-miR-4728-5p, miR-652-5p is hsa-miR-652-5p, miR-4257 is hsa-miR-4257, miR-6785-5p is hsa-miR-6785-5p, miR-7110-5p is hsa-miR-7110-5p, miR-6887-5p is hsa-miR-6887-5p, miR-887-3p is hsa-miR-887-3p, miR-1228-5p is hsa-miR-1228-5p, miR-5572 is hsa-miR-5572, miR-6782-5p is hsa-miR-6782-5p, miR-4298 is hsa-miR-4298, miR-6786-5p is hsa-miR-6786-5p, miR-5010-5p is hsa-miR-5010-5p, miR-6087 is hsa-miR-6087, miR-6765-5p is hsa-miR-6765-5p, miR-6732-5p is hsa-miR-6732-5p,miR-6787-5p is hsa-miR-6787-5p, miR-6737-5p is hsa-miR-6737-5p, miR-128-2-5p is hsa-miR-128-2-5p, miR-4270 is hsa-miR-4270, miR-6861-5p is hsa-miR-6861-5p, miR-6756-5p is hsa-miR-6756-5p, miR-1229-5p is hsa-miR-1229-5p, miR-6891-5p is hsa-miR-6891-5p, miR-6848-5p is hsa-miR-6848-5p, miR-1237-5p is hsa-miR-1237-5p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-1233-5p is hsa-miR-1233-5p, miR-211-3p is hsa-miR-211-3p, miR-4758-5p is hsa-miR-4758-5p, miR-614 is hsa-miR-614, miR-6746-5p is hsa-miR-6746-5p, miR-1915-5p is hsa-miR-1915-5p, miR-4688 is hsa-miR-4688, miR-3917 is hsa-miR-3917, miR-5787 is hsa-miR-5787, miR-4632-5p is hsa-miR-4632-5p, miR-6126 is hsa-miR-6126, miR-135a-3p is hsa-miR-135a-3p, miR-8063 is hsa-miR-8063, miR-5698 is hsa-miR-5698, miR-6089 is hsa-miR-6089, miR-498 is hsa-miR-498, miR-296-3p is hsa-miR-296-3p, miR-4419b is hsa-miR-4419b, miR-6802-5p is hsa-miR-6802-5p, miR-6829-5p is hsa-miR-6829-5p, miR-6803-5p is hsa-miR-6803-5p, miR-1199-5p is hsa-miR-1199-5p, miR-6840-3p is hsa-miR-6840-3p,miR-6752-5p is hsa-miR-6752-5p, miR-6798-5p is hsa-miR-6798-5p, miR-6131 is hsa-miR-6131, miR-4667-5p is hsa-miR-4667-5p, miR-6510-5p is hsa-miR-6510-5p, miR-4690-5p is hsa-miR-4690-5p, miR-920 is hsa-miR-920, miR-23b-3p is hsa-miR-23b-3p, miR-4448 is hsa-miR-4448, miR-2110 is hsa-miR-2110, miR-4706 is hsa-miR-4706, miR-7845-5p is hsa-miR-7845-5p, miR-6808-5p is hsa-miR-6808-5p, miR-4447 is hsa-miR-4447, miR-6869-5p is hsa-miR-6869-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6511a-5p is hsa-miR-6511a-5p, miR-6824-5p is hsa-miR-6824-5p, miR-6766-3p is hsa-miR-6766-3p, miR-6511a-5p is hsa-miR-6511a-5p, miR-6749-5p is hsa-miR-6749-5p, the device according to (7).
[0035] (9) The nucleic acid is a polynucleotide represented by any one of the following (a) to (e): (a) A polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases. (b) A polynucleotide containing a base sequence represented by any one of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250. (c) A polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250 or a nucleotide sequence complementary to a nucleotide sequence in which u is t in the said nucleotide sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive nucleotides, (d) A polynucleotide containing a nucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250 or a nucleotide sequence complementary to a nucleotide sequence in which u is t in the said nucleotide sequence, and (e) A polynucleotide that hybridizes with any of the polynucleotides of (a) to (d) above under stringent conditions, The device according to (7) or (8), which is a polynucleotide selected from the group consisting of.
[0036] (10) The device is miR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125, miR-3178, miR-3196, miR-8069, miR-4723-5p, miR-4746-3p, miR-4689, miR-6816-5p, miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p, miR-6875-5p, miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p, miR-4695-5p, miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p, miR-3185, miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p, miR-1343-3p, miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p, miR-5100, miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718, miR-6780b-5p, miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p, miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a, miR-6791-5p, miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449, miR-4707-3p, miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p, miR-204-3p, miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p, miR-675-5p, miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p, miR-3162-5p, miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p, miR-7113-3p, miR-6850-5p, another early pancreatic cancer or pancreatic cancer precursor lesion marker.a nucleic acid that can specifically bind to at least one polynucleotide selected from the group consisting of miR-6799-5p, miR-6768-5p, miR-92b-5p, miR-3679-5p, miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513, miR-6781-5p, miR-4649-5p, miR-6775-5p, miR-4651, miR-3195, miR-6726-5p, miR-6872-3p, miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975, miR-6821-5p, miR-4534, miR-619-5p, miR-7107-5p, miR-1228-3p, miR-6774-5p, miR-6805-5p, miR-23a-3p, miR-4665-5p, miR-4505, miR-4638-5p, miR-24-3p, miR-3135b, miR-4745-5p, miR-128-1-5p, miR-4476, miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141, miR-3188, miR-4281, miR-5196-5p, miR-6880-5p, miR-3960, miR-3648, miR-6721-5p, miR-4492, miR-744-5p, miR-7704, miR-4749-5p, miR-762, miR-6836-3p, miR-6727-5p, miR-4739, miR-7977, miR-4484, miR-6515-3p, miR-373-5p, miR-4258, miR-4674, miR-3180, miR-6076, miR-1238-5p, miR-4463, miR-4486, miR-4730, miR-4286, and miR-4739, the device according to any one of (7)-(9).
[0037] (11) miR-1908-5p is hsa-miR-1908-5p, miR-6729-5p is hsa-miR-6729-5p, miR-5195-3p is hsa-miR-5195-3p, miR-638 is hsa-miR-638, miR-6125 is hsa-miR-6125, miR-3178 is hsa-miR-3178, miR-3196 is hsa-miR-3196, miR-8069 is hsa-miR-8069, miR-4723-5p is hsa-miR-4723-5p, miR-4746-3p is hsa-miR-4746-3p, miR-4689 is hsa-miR-4689, miR-6816-5p is hsa-miR-6816-5p, miR-6757-5p is hsa-miR-6757-5p, miR-7109-5p is hsa-miR-7109-5p, miR-6724-5p is hsa-miR-6724-5p, miR-1225-3p is hsa-miR-1225-3p, miR-6875-5p is hsa-miR-6875-5p, miR-7108-5p is hsa-miR-7108-5p, miR-4508 is hsa-miR-4508, miR-6085 is hsa-miR-6085, miR-6779-5p is hsa-miR-6779-5p, miR-642a-3p is hsa-miR-642a-3p, miR-4695-5p is hsa-miR-4695-5p, miR-7847-3p is hsa-miR-7847-3p, miR-3197 is hsa-miR-3197, miR-6769b-5p is hsa-miR-6769b-5p, miR-7641 is hsa-miR-7641, miR-187-5p is hsa-miR-187-5p, miR-3185 is hsa-miR-3185, miR-2861 is hsa-miR-2861, miR-3940-5p is hsa-miR-3940-5p, miR-1203 is hsa-miR-1203, miR-615-5p is hsa-miR-615-5p, miR-4787-5p is hsa-miR-4787-5p,miR-1343-3p is hsa-miR-1343-3p, miR-6813-5p is hsa-miR-6813-5p, miR-1225-5p is hsa-miR-1225-5p, miR-602 is hsa-miR-602, miR-4488 is hsa-miR-4488, miR-125a-3p is hsa-miR-125a-3p, miR-5100 is hsa-miR-5100, miR-4294 is hsa-miR-4294, miR-1231 is hsa-miR-1231, miR-6765-3p is hsa-miR-6765-3p, miR-4442 is hsa-miR-4442, miR-718 is hsa-miR-718, miR-6780b-5p is hsa-miR-6780b-5p, miR-6090 is hsa-miR-6090, miR-6845-5p is hsa-miR-6845-5p, miR-4741 is hsa-miR-4741, miR-4467 is hsa-miR-4467, miR-4707-5p is hsa-miR-4707-5p, miR-4271 is hsa-miR-4271, miR-4673 is hsa-miR-4673, miR-3184-5p is hsa-miR-3184-5p, miR-1469 is hsa-miR-1469, miR-4640-5p is hsa-miR-4640-5p, miR-663a is hsa-miR-663a, miR-6791-5p is hsa-miR-6791-5p, miR-6826-5p is hsa-miR-6826-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-1915-3p is hsa-miR-1915-3p, miR-4417 is hsa-miR-4417, miR-4449 is hsa-miR-4449, miR-4707-3p is hsa-miR-4707-3p, miR-3180-3p is hsa-miR-3180-3p, miR-5585-3p is hsa-miR-5585-3p, miR-1268a is hsa-miR-1268a, miR-8072 is hsa-miR-8072,miR-296-5p is hsa-miR-296-5p, miR-204-3p is hsa-miR-204-3p, miR-4454 is hsa-miR-4454, miR-6722-3p is hsa-miR-6722-3p, miR-1290 is hsa-miR-1290, miR-3622a-5p is hsa-miR-3622a-5p, miR-939-5p is hsa-miR-939-5p, miR-675-5p is hsa-miR-675-5p, miR-3131 is hsa-miR-3131, miR-4648 is hsa-miR-4648, miR-1268b is hsa-miR-1268b, miR-6741-5p is hsa-miR-6741-5p, miR-6893-5p is hsa-miR-6893-5p, miR-3162-5p is hsa-miR-3162-5p, miR-642b-3p is hsa-miR-642b-3p, miR-4734 is hsa-miR-4734, miR-150-3p is hsa-miR-150-3p, miR-8089 is hsa-miR-8089, miR-6805-3p is hsa-miR-6805-3p, miR-7113-3p is hsa-miR-7113-3p, miR-6850-5p is hsa-miR-6850-5p, miR-6799-5p is hsa-miR-6799-5p, miR-6768-5p is hsa-miR-6768-5p, miR-92b-5p is hsa-miR-92b-5p, miR-3679-5p is hsa-miR-3679-5p, miR-4792 is hsa-miR-4792, miR-3656 is hsa-miR-3656, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-4466 is hsa-miR-4466, miR-4513 is hsa-miR-4513, miR-6781-5p is hsa-miR-6781-5p, miR-4649-5p is hsa-miR-4649-5p, miR-6775-5p is hsa-miR-6775-5p, miR-4651 is hsa-miR-4651, miR-3195 is hsa-miR-3195,miR-6726-5p is hsa-miR-6726-5p, miR-6872-3p is hsa-miR-6872-3p, miR-371a-5p is hsa-miR-371a-5p, miR-6777-5p is hsa-miR-6777-5p, miR-6789-5p is hsa-miR-6789-5p, miR-7975 is hsa-miR-7975, miR-6821-5p is hsa-miR-6821-5p, miR-4534 is hsa-miR-4534, miR-619-5p is hsa-miR-619-5p, miR-7107-5p is hsa-miR-7107-5p, miR-1228-3p is hsa-miR-1228-3p, miR-6774-5p is hsa-miR-6774-5p, miR-6805-5p is hsa-miR-6805-5p, miR-23a-3p is hsa-miR-23a-3p, miR-4665-5p is hsa-miR-4665-5p, miR-4505 is hsa-miR-4505, miR-4638-5p is hsa-miR-4638-5p, miR-24-3p is hsa-miR-24-3p, miR-3135b is hsa-miR-3135b, miR-4745-5p is hsa-miR-4745-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-4476 is hsa-miR-4476, miR-4687-3p is hsa-miR-4687-3p, miR-3665 is hsa-miR-3665, miR-6806-5p is hsa-miR-6806-5p, miR-3937 is hsa-miR-3937, miR-711 is hsa-miR-711, miR-3141 is hsa-miR-3141, miR-3188 is hsa-miR-3188, miR-4281 is hsa-miR-4281, miR-5196-5p is hsa-miR-5196-5p, miR-6880-5p is hsa-miR-6880-5p, miR-3960 is hsa-miR-3960, miR-3648 is hsa-miR-3648, miR-6721-5p is hsa-miR-6721-5p,miR-4492 is hsa-miR-4492, miR-744-5p is hsa-miR-744-5p, miR-7704 is hsa-miR-7704, miR-4749-5p is hsa-miR-4749-5p, miR-762 is hsa-miR-762, miR-6836-3p is hsa-miR-6836-3p, miR-6727-5p is hsa-miR-6727-5p, miR-4739 is hsa-miR-4739, miR-7977 is hsa-miR-7977, miR-4484 is hsa-miR-4484, miR-6515-3p is hsa-miR-6515-3p, miR-373-5p is hsa-miR-373-5p, miR-4258 is hsa-miR-4258, miR-4674 is hsa-miR-4674, miR-3180 is hsa-miR-3180, miR-6076 is hsa-miR-6076, miR-1238-5p is hsa-miR-1238-5p, miR-4463 is hsa-miR-4463, miR-4486 is hsa-miR-4486, miR-4730 is hsa-miR-4730, miR-4286 is hsa-miR-4286, miR-4739 is hsa-miR-4739, the device according to (10).
[0038] (12) The nucleic acid is a polynucleotide represented by any one of the following (f) to (j): (f) A polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases. (g) A polynucleotide containing a base sequence represented by any one of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249. (h) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a base sequence complementary to a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (i) A polynucleotide containing a base sequence represented by any of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a base sequence complementary to a base sequence in which u is t in the base sequence, and (j) A polynucleotide that hybridizes with any of the polynucleotides of (f) to (i) above under stringent conditions, The device according to (10) or (11), which is a polynucleotide selected from the group consisting of.
[0039] (13) The device according to any of (7) to (12), wherein the device is a device for measurement by a hybridization technique.
[0040] (14) The device according to (13), wherein the hybridization technique is a nucleic acid array technique.
[0041] (15) Measuring the expression level of a target nucleic acid in a sample from a subject using the kit according to any of (1) to (6) or the device according to any of (7) to (14), and using the measured expression level and the control expression level of a healthy subject measured in the same manner, evaluating in vitro whether the subject is suffering from early pancreatic cancer or a pancreatic cancer precursor lesion, or not suffering from early pancreatic cancer or a pancreatic cancer precursor lesion, and thereby detecting the presence or absence of early pancreatic cancer or a pancreatic cancer precursor lesion in the subject. A method for detecting early pancreatic cancer or a pancreatic cancer precursor lesion in a subject, which includes.
[0042] (16) Measuring the expression level of a target gene in a specimen of a subject using the kit according to any one of (1) to (6) or the device according to any one of (7) to (14), and using the gene expression level of a specimen derived from a subject known to have early pancreatic cancer or a pancreatic cancer precursor lesion and the gene expression level of a specimen derived from a healthy subject as teacher samples, and substituting the expression level of the target gene in the specimen derived from the subject into a discriminant formula (discriminant function) capable of distinguishing early pancreatic cancer or a pancreatic cancer precursor lesion from health, thereby evaluating the presence or absence of early pancreatic cancer or a pancreatic cancer precursor lesion. A method for detecting early pancreatic cancer or a pancreatic cancer precursor lesion in a subject, comprising the above steps.
[0043] (17) The method according to (15) or (16), wherein the subject is a human.
[0044] (18) The method according to any one of (15) to (17), wherein the specimen is blood, serum or plasma.
[0045] <Definition of Terms> The terms used in this specification have the following definitions.
[0046] As used herein, "pancreatic cancer" refers to invasive ductal carcinomas. Specifically, it includes papillary adenocarcinoma, tubular adenocarcinoma, poorly differentiated adenocarcinoma, adenosquamous carcinoma, mucious carcinoma, anaplastic carcinoma, etc. formed in the pancreas ("Pancreatic Cancer Treatment Guidelines", 6th Revised Edition, 2013, Japan Pancreatic Society, Kanehara Publishing (Tokyo, Japan), p27 - 28).
[0047] As used herein, "pancreatic cancer precursor lesion" refers to exocrine neoplasms formed in the pancreas. Specifically, it includes serous cystic neoplasms (SCNs), serous cystadenoma (SCA), serous cystadenocarcinoma (SCC), mucinous cystic neoplasms (MCNs), mucinous cystadenoma (MCA), mucinous cystadenocarcinoma (MCC), intraductal papillary-mucinous neoplasms (IPMNs), intraductal papillary-mucinous adenoma (IPMA), intraductal papillary-mucinous carcinoma (IPMC), etc. ("Pancreatic Cancer Treatment Guidelines", 6th Revised Edition, 2013, Japanese Pancreatic Society, Kanehara Shuppan (Tokyo, Japan), p24-27).
[0048] As used herein, "degree of progression of pancreatic cancer" is classified into stage 0, IA, IB, IIA, IIB, III, IVa, and IVb according to the local progression of the main tumor, lymph node metastasis, distant metastasis, etc. ("Pancreatic Cancer Treatment Guidelines", 6th Revised Edition, 2013, Japanese Pancreatic Society, Kanehara Shuppan (Tokyo, Japan), p55-57).
[0049] As used herein, "early-stage pancreatic cancer" refers to pancreatic cancer at stage 0, IA, IB, IIA, and IIB.
[0050] As used herein, "advanced pancreatic cancer" refers to pancreatic cancer at stage III, IVa, and IVb.
[0051] As used herein, "benign disease" refers to a non-malignant tumor disease related to an organ.
[0052] In addition, the notations using abbreviations such as "nucleotide", "polynucleotide", "DNA", and "RNA" used in this specification shall follow the "Guidelines for the Preparation of Specifications, etc. Containing Base Sequences or Amino Acid Sequences" (edited by the Japan Patent Office) and the common practice in the art.
[0053] In this specification, the term "polynucleotide" is used for nucleic acids including any of RNA, DNA, and RNA / DNA (chimeric). Note that the above DNA includes any of cDNA, genomic DNA, and synthetic DNA. Also, the above RNA includes any of total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA, and synthetic RNA. In this specification, "synthetic DNA" and "synthetic RNA" refer to DNA and RNA artificially produced based on a predetermined base sequence (which may be either a natural-type sequence or a non-natural-type sequence), for example, using an automatic nucleic acid synthesizer. In this specification, the term "non-natural-type sequence" is intended to be used in a broad sense and includes sequences different from natural-type sequences, such as sequences containing substitutions, deletions, insertions, and / or additions of one or more nucleotides (i.e., mutant sequences), sequences containing one or more modified nucleotides (i.e., modified sequences), and the like. Also, in this specification, polynucleotide is used interchangeably with nucleic acid.
[0054] In this specification, the term "fragment" refers to a polynucleotide having a base sequence of a continuous part of a polynucleotide, and desirably has a length of 15 bases or more, preferably 17 bases or more, more preferably 19 bases or more.
[0055] In this specification, the term "gene" is used to intend to include not only RNA and double-stranded DNA, but also each single-stranded DNA such as the positive strand (or sense strand) or the complementary strand (or antisense strand) constituting them. Also, it is not particularly limited by its length.
[0056] Therefore, in this specification, unless otherwise specified, the term "gene" includes double-stranded DNA containing human genomic DNA, single-stranded DNA (sense strand), single-stranded DNA having a sequence complementary to the sense strand (complementary strand) (e.g., cDNA), microRNA (miRNA), and fragments thereof, as well as transcripts thereof. The "gene" is not limited to the "gene" represented by a specific base sequence (or sequence number), but also includes "nucleic acids" encoding RNAs having the same biological function as the RNAs encoded by these, such as homologs (i.e., homologs or orthologs), mutants such as gene polymorphisms, and derivatives. Specific examples of the "nucleic acids" encoding such homologs, mutants, or derivatives include "nucleic acids" having a base sequence that hybridizes with the complementary sequence of the base sequence represented by any of SEQ ID NOs: 1 to 812 or a base sequence in which u is t in the base sequence under the stringent conditions described later. Note that the "gene" is not limited by the distinction of functional regions and can include, for example, an expression control region, a coding region, an exon, or an intron. Also, the "gene" may be contained in cells, may exist alone outside cells after being released extracellularly, or may be encapsulated in vesicles called exosomes.
[0057] As used herein, the term "exosome" (also known as "exosome") refers to vesicles enclosed by a lipid bilayer membrane secreted from cells. Exosomes are derived from multivesicular endosomes and may contain biological substances such as "genes" such as RNA and DNA and proteins when released into the extracellular environment. Exosomes are known to be contained in body fluids such as blood, serum, plasma, and lymph.
[0058] As used herein, the term "transcript" refers to RNA synthesized using the DNA sequence of a gene as a template. RNA polymerase binds to a site called a promoter upstream of the gene and synthesizes RNA by binding ribonucleotides to the 3'-end so as to be complementary to the base sequence of the DNA. This RNA includes not only the gene itself, but also the entire sequence from the transcription start point to the end of the polyA sequence, including expression control regions, coding regions, exons or introns.
[0059] In addition, as used herein, the term "microRNA (miRNA)" refers to a non-coding RNA of 15 to 25 bases that is transcribed as an RNA precursor having a hairpin-like structure, cleaved by a dsRNA cleaving enzyme having RNase III cleavage activity, incorporated into a protein complex called RISC, and involved in translational repression of mRNA, unless otherwise specified. The term "miRNA" as used herein includes not only "miRNA" represented by a specific base sequence (or SEQ ID NO.), but also precursors (pre-miRNA, pri-miRNA) of the "miRNA", miRNAs having biological functions equivalent thereto, such as homologs (i.e., homologs or orthologs), mutants such as gene polymorphisms, and derivatives. Such precursors, homologs, mutants or derivatives can be specifically identified by miRBase release 20 (http: / / www.mirbase.org / ) and hybridize with the complementary sequence of any of the specific base sequences represented by SEQ ID NOs. 1 to 812 under the stringent conditions described below. Furthermore, the term "miRNA" as used herein may be a gene product of an miR gene, and such a gene product includes mature miRNA (e.g., a non-coding RNA of 15 to 25 bases, or 19 to 25 bases, involved in translational repression of mRNA as described above) or miRNA precursor (e.g., pre-miRNA or pri-miRNA as described above).
[0060] As used herein, the term "probe" includes a polynucleotide and / or a polynucleotide complementary thereto that is used to specifically detect an RNA produced by gene expression or a polynucleotide derived therefrom.
[0061] As used herein, the term "primer" includes a polynucleotide and / or a polynucleotide complementary thereto that specifically recognizes and amplifies an RNA produced by gene expression or a polynucleotide derived therefrom.
[0062] Here, the complementary polynucleotide (complementary strand, reverse strand) means a polynucleotide having a base complementary relationship based on the base pair relationship such as A:T(U), G:C with respect to the full-length sequence or a partial sequence of a polynucleotide consisting of the base sequence defined by any of SEQ ID NOs: 1 to 812, or a base sequence in which u is t in the said base sequence (herein, this is referred to as the sense strand for convenience). Also, the description of "a polynucleotide consisting of a complementary base sequence" for the base sequence represented by any of SEQ ID NOs: 1 to 812 or a base sequence in which u is t in the said base sequence is basically understood in the same manner.
[0063] As used herein, the term "stringent conditions" refers to conditions under which a nucleic acid probe hybridizes to its target sequence to a detectably greater extent (e.g., a measurement value of the average of the background measurement value + 2 times the standard error of the background measurement value or more) than to other sequences. Stringent conditions are sequence-dependent and vary depending on the environment in which hybridization is performed. By controlling the stringency of hybridization and / or washing conditions, a target sequence that is 100% complementary to the nucleic acid probe can be identified. Specific examples of "stringent conditions" are described below.
[0064] As used herein, the term "Tm value" means the temperature at which the double-stranded portion of a polynucleotide denatures into single strands and the double strands and single strands are present in a ratio of 1:1.
[0065] As used herein, the term "variant" in the case of nucleic acids refers to natural variants resulting from polymorphisms, mutations, etc., or the nucleotide sequences of any of SEQ ID NOs: 1 to 812, or nucleotide sequences in which u is t in said nucleotide sequences, or variants including deletion, substitution, addition or insertion of one or more (e.g., 1 to several) bases in a partial sequence thereof, or variants showing about 90% or more, about 95% or more, about 97% or more, about 98% or more, about 99% or more sequence identity with each of said nucleotide sequences or a partial sequence thereof, or nucleic acids that hybridize with a polynucleotide or oligonucleotide containing said nucleotide sequence or a partial sequence thereof under the stringent conditions defined above.
[0066] As used herein, the term "several" means an integer of about 10, 9, 8, 7, 6, 5, 4, 3 or 2.
[0067] As used herein, variants can be prepared using well-known techniques such as site-directed mutagenesis and mutagenesis methods using the PCR method.
[0068] As used herein, "% identity" can be determined using protein or gene search systems such as BLAST and FASTA described above, with or without introducing gaps (Zheng Zhang et al., 2000, J. Comput. Biol., Vol. 7, p203-214; Altschul, S.F. et al., 1990, Journal of Molecular Biology, Vol. 215, p403-410; Pearson, W.R. et al., 1988, Proc. Natl. Acad. Sci. U.S.A., Vol. 85, p2444-2448).
[0069] As used herein, the term "derivative" means a modified nucleic acid, including, without limitation, a labeled derivative such as a fluorophore, a derivative containing a modified nucleotide (e.g., a nucleotide containing a group such as a halogen, an alkyl such as methyl, an alkoxy such as methoxy, thio, carboxymethyl, etc., and a reconfigured nucleotide or base, saturation of a double bond, deamination, substitution of an oxygen molecule with a sulfur molecule, etc.), a PNA (peptide nucleic acid; Nielsen, P.E. et al., 1991, Science, Vol. 254, p1497 - 500), an LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, p5401 - 5404), etc.
[0070] As used herein, the "nucleic acid" that can specifically bind to a polynucleotide selected from the above miRNA which is a marker for early pancreatic cancer or pancreatic cancer precursor lesions is a synthesized or prepared nucleic acid, specifically including a "nucleic acid probe" or a "primer", and is used directly or indirectly for detecting the presence or absence of early pancreatic cancer or pancreatic cancer precursor lesions in a subject, or for diagnosing the presence or absence of susceptibility to early pancreatic cancer or pancreatic cancer precursor lesions, the degree of susceptibility, the presence or absence and degree of improvement of early pancreatic cancer or pancreatic cancer precursor lesions, or for screening candidate substances useful for the prevention, improvement or treatment of early pancreatic cancer or pancreatic cancer precursor lesions. These include nucleotides, oligonucleotides and polynucleotides that can specifically recognize and bind to a transcript represented by any of SEQ ID NOs: 1 - 812 or a cDNA - synthesized nucleic acid thereof in a sample such as a biological sample, particularly a body fluid such as blood or urine, in relation to the development of early pancreatic cancer or pancreatic cancer precursor lesions. These nucleotides, oligonucleotides and polynucleotides can be effectively used as a probe for detecting the above - mentioned gene expressed in vivo, such as in tissues or cells, and as a primer for amplifying the above - mentioned gene expressed in vivo.
[0071] As used herein, the term "detection" can be replaced with the terms "inspection", "measurement", "judgment", or "judgment assistance". Further, as used herein, the term "evaluation" is used in the sense of including assisting in diagnosis or evaluation based on inspection results or measurement results.
[0072] As used herein, the term "subject" means mammals such as humans, primates including chimpanzees, pet animals such as dogs and cats, livestock animals such as cows, horses, sheep, and goats, rodents such as mice and rats, and animals bred in zoos. A preferred subject is a human. Also, a "healthy subject" also means such a mammal that is not suffering from the cancer to be detected. A preferred healthy subject is a human.
[0073] As used herein, "P" or "P-value" refers to the probability that a statistic more extreme than the statistic actually calculated from the data is observed under the null hypothesis in a statistical test. Therefore, the smaller "P" or "P-value" is, the more likely it is considered that there is a significant difference between the comparison targets.
[0074] As used herein, "sensitivity" means the value of (number of true positives) / (number of true positives + number of false negatives). If the sensitivity is high, it becomes possible to detect early pancreatic cancer or pancreatic cancer precursor lesions at an early stage, leading to complete resection of the cancerous part and a reduction in the recurrence rate.
[0075] As used herein, "specificity" means (number of true negatives) / (number of true negatives + number of false positives). If the specificity is high, it prevents the unnecessary additional examinations due to misclassifying healthy subjects as patients with early pancreatic cancer or pancreatic cancer precursor lesions, leading to a reduction in the burden on patients and a reduction in medical costs.
[0076] As used herein, "accuracy" means the value of (number of true positives + number of true negatives) / (total number of cases). Accuracy indicates the proportion of correct discrimination results for all specimens and is the first index for evaluating the detection performance.
[0077] As used herein, the "sample" to be determined, detected or diagnosed refers to tissues and biological materials in which the genes of the present invention exhibit changes in expression along with the occurrence of early pancreatic cancer or pancreatic cancer precursor lesions, the progression of early pancreatic cancer or pancreatic cancer precursor lesions, or the exertion of therapeutic effects on early pancreatic cancer or pancreatic cancer precursor lesions. Specifically, it refers to pancreatic tissues and the surrounding blood vessels, lymph nodes and organs, as well as organs suspected of metastasis, skin, and body fluids such as blood, urine, saliva, sweat, tissue exudates, serum and plasma prepared from blood, and further feces, hair, etc. Furthermore, it refers to biological samples extracted from these, specifically genes such as RNA and miRNA.
[0078] As used herein, the term "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" includes the hsa-miR-6784-5p gene (miRBase Accession No. MIMAT0027468) described in SEQ ID NO: 1, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6784-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6784" (miRBase Accession No. MI0022629, SEQ ID NO: 251).
[0079] As used herein, the term "hsa-miR-1181 gene" or "hsa-miR-1181" includes the hsa-miR-1181 gene (miRBase Accession No. MIMAT0005826) described in SEQ ID NO: 2, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Subramanian S et al., 2008, Oncogene, 27, p2015-2026. Also, "hsa-miR-1181" is known to have a hairpin-like structure as its precursor, "hsa-mir-1181" (miRBase Accession No. MI0006274, SEQ ID NO: 252).
[0080] As used herein, the term "hsa-miR-671-5p gene" or "hsa-miR-671-5p" includes the hsa-miR-671-5p gene described in SEQ ID NO: 3 (miRBase Accession No. MIMAT0003880), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, 16, p1289-1298. Also, "hsa-miR-671-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-671" (miRBase Accession No. MI0003760, SEQ ID NO: 253).
[0081] As used herein, the term "hsa-miR-6857-5p gene" or "hsa-miR-6857-5p" includes the hsa-miR-6857-5p gene described in SEQ ID NO: 4 (miRBase Accession No. MIMAT0027614), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6857-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6857" (miRBase Accession No. MI0022703, SEQ ID NO: 254).
[0082] As used herein, the term "hsa-miR-4276 gene" or "hsa-miR-4276" includes the hsa-miR-4276 gene described in SEQ ID NO: 5 (miRBase Accession No. MIMAT0016904), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4276" is known to have a hairpin-like structure as its precursor, "hsa-mir-4276" (miRBase Accession No. MI0015882, SEQ ID NO: 255).
[0083] As used herein, the term "hsa-miR-1914-3p gene" or "hsa-miR-1914-3p" includes the hsa-miR-1914-3p gene described in SEQ ID NO: 6 (miRBase Accession No. MIMAT0007890), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, 26, p2496 - 2505. Also, "hsa-miR-1914-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1914" (miRBase Accession No. MI0008335, SEQ ID NO: 256).
[0084] As used herein, the terms "hsa-miR-149-3p gene" or "hsa-miR-149-3p" include the hsa-miR-149-3p gene described in SEQ ID NO: 7 (miRBase Accession No. MIMAT0004609), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, 12, p735-739. Also, "hsa-miR-149-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-149" (miRBase Accession No. MI0000478, SEQ ID NO: 257).
[0085] As used herein, the terms "hsa-miR-937-5p gene" or "hsa-miR-937-5p" include the hsa-miR-937-5p gene described in SEQ ID NO: 8 (miRBase Accession No. MIMAT0022938), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, 67, p6031-6043. Also, "hsa-miR-937-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-937" (miRBase Accession No. MI0005759, SEQ ID NO: 258).
[0086] As used herein, the term "hsa-miR-4675 gene" or "hsa-miR-4675" includes the hsa-miR-4675 gene (miRBase Accession No. MIMAT0019757) described in SEQ ID NO: 9, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4675" is known to have a hairpin-like structure as its precursor, "hsa-mir-4675" (miRBase Accession No. MI0017306, SEQ ID NO: 259).
[0087] As used herein, the term "hsa-miR-6795-5p gene" or "hsa-miR-6795-5p" includes the hsa-miR-6795-5p gene (miRBase Accession No. MIMAT0027490) described in SEQ ID NO: 10, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6795-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6795" (miRBase Accession No. MI0022640, SEQ ID NO: 260).
[0088] As used herein, the terms "hsa-miR-4731-5p gene" or "hsa-miR-4731-5p" include the hsa-miR-4731-5p gene described in SEQ ID NO: 11 (miRBase Accession No. MIMAT0019853), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4731-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4731" (miRBase Accession No. MI0017368, SEQ ID NO: 261).
[0089] As used herein, the terms "hsa-miR-5090 gene" or "hsa-miR-5090" include the hsa-miR-5090 gene described in SEQ ID NO: 12 (miRBase Accession No. MIMAT0021082), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ding N et al., 2011, J Radiat Res, 52, p425-432. Also, "hsa-miR-5090" is known to have a hairpin-like structure as its precursor, "hsa-mir-5090" (miRBase Accession No. MI0017979, SEQ ID NO: 262).
[0090] As used herein, the term "hsa-miR-3620-5p gene" or "hsa-miR-3620-5p" includes the hsa-miR-3620-5p gene described in SEQ ID NO: 13 (miRBase Accession No. MIMAT0022967), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, 8, p58. Also, "hsa-miR-3620-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3620" (miRBase Accession No. MI0016011, SEQ ID NO: 263).
[0091] As used herein, the term "hsa-miR-1343-5p gene" or "hsa-miR-1343-5p" includes the hsa-miR-1343-5p gene described in SEQ ID NO: 14 (miRBase Accession No. MIMAT0027038), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-1343-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 264).
[0092] As used herein, the terms "hsa-miR-6717-5p gene" or "hsa-miR-6717-5p" include the hsa-miR-6717-5p gene described in SEQ ID NO: 15 (miRBase Accession No. MIMAT0025846), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Also, "hsa-miR-6717-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6717" (miRBase Accession No. MI0022551, SEQ ID NO: 265).
[0093] As used herein, the terms "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" include the hsa-miR-6825-5p gene described in SEQ ID NO: 16 (miRBase Accession No. MIMAT0027550), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Also, "hsa-miR-6825-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6825" (miRBase Accession No. MI0022670, SEQ ID NO: 266).
[0094] As used herein, the terms "hsa-miR-6738-5p gene" or "hsa-miR-6738-5p" include the hsa-miR-6738-5p gene described in SEQ ID NO: 17 (miRBase Accession No. MIMAT0027377), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6738-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6738" (miRBase Accession No. MI0022583, SEQ ID NO: 267).
[0095] As used herein, the terms "hsa-miR-6769a-5p gene" or "hsa-miR-6769a-5p" include the hsa-miR-6769a-5p gene described in SEQ ID NO: 18 (miRBase Accession No. MIMAT0027438), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6769a-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6769a" (miRBase Accession No. MI0022614, SEQ ID NO: 268).
[0096] As used herein, the terms "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" include the hsa-miR-4728-5p gene (miRBase Accession No. MIMAT0019849) described in SEQ ID NO: 19, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4728-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4728" (miRBase Accession No. MI0017365, SEQ ID NO: 269).
[0097] As used herein, the terms "hsa-miR-652-5p gene" or "hsa-miR-652-5p" include the hsa-miR-652-5p gene (miRBase Accession No. MIMAT0022709) described in SEQ ID NO: 20, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-652-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-652" (miRBase Accession No. MI0003667, SEQ ID NO: 270).
[0098] As used herein, the term "hsa-miR-4257 gene" or "hsa-miR-4257" includes the hsa-miR-4257 gene (miRBase Accession No. MIMAT0016878) described in SEQ ID NO: 21, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4257" is known to have a hairpin-like structure as its precursor, "hsa-mir-4257" (miRBase Accession No. MI0015856, SEQ ID NO: 271).
[0099] As used herein, the term "hsa-miR-6785-5p gene" or "hsa-miR-6785-5p" includes the hsa-miR-6785-5p gene (miRBase Accession No. MIMAT0027470) described in SEQ ID NO: 22, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6785-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6785" (miRBase Accession No. MI0022630, SEQ ID NO: 272).
[0100] As used herein, the terms "hsa-miR-7110-5p gene" or "hsa-miR-7110-5p" include the hsa-miR-7110-5p gene (miRBase Accession No. MIMAT0028117) described in SEQ ID NO: 23, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-7110-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7110" (miRBase Accession No. MI0022961, SEQ ID NO: 273).
[0101] As used herein, the terms "hsa-miR-6887-5p gene" or "hsa-miR-6887-5p" include the hsa-miR-6887-5p gene (miRBase Accession No. MIMAT0027674) described in SEQ ID NO: 24, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6887-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6887" (miRBase Accession No. MI0022734, SEQ ID NO: 274).
[0102] As used herein, the terms "hsa-miR-887-3p gene" or "hsa-miR-887-3p" include the hsa-miR-887-3p gene described in SEQ ID NO: 25 (miRBase Accession No. MIMAT0004951), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, 16, p1289-1298. Also, "hsa-miR-887-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-887" (miRBase Accession No. MI0005562, SEQ ID NO: 275).
[0103] As used herein, the terms "hsa-miR-1228-5p gene" or "hsa-miR-1228-5p" include the hsa-miR-1228-5p gene described in SEQ ID NO: 26 (miRBase Accession No. MIMAT0005582), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336. Also, "hsa-miR-1228-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 276).
[0104] As used herein, the term "hsa-miR-5572 gene" or "hsa-miR-5572" includes the hsa-miR-5572 gene described in SEQ ID NO: 27 (miRBase Accession No. MIMAT0022260), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Tandon M et al., 2012, Oral Dis, 18, p127-131. Also, "hsa-miR-5572" is known to have a hairpin-like structure as its precursor, "hsa-mir-5572" (miRBase Accession No. MI0019117, SEQ ID NO: 277).
[0105] As used herein, the term "hsa-miR-6782-5p gene" or "hsa-miR-6782-5p" includes the hsa-miR-6782-5p gene described in SEQ ID NO: 28 (miRBase Accession No. MIMAT0027464), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6782-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6782" (miRBase Accession No. MI0022627, SEQ ID NO: 278).
[0106] As used herein, the term "hsa-miR-4298 gene" or "hsa-miR-4298" includes the hsa-miR-4298 gene described in SEQ ID NO: 29 (miRBase Accession No. MIMAT0016852), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4298" is known to have a hairpin-like structure as its precursor, "hsa-mir-4298" (miRBase Accession No. MI0015830, SEQ ID NO: 279).
[0107] As used herein, the terms "hsa-miR-6786-5p gene" or "hsa-miR-6786-5p" include the hsa-miR-6786-5p gene described in SEQ ID NO: 30 (miRBase Accession No. MIMAT0027472), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6786-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6786" (miRBase Accession No. MI0022631, SEQ ID NO: 280).
[0108] As used herein, the terms "hsa-miR-5010-5p gene" or "hsa-miR-5010-5p" include the hsa-miR-5010-5p gene described in SEQ ID NO: 31 (miRBase Accession No. MIMAT0021043), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Hansen TB et al., 2011, RNA Biol, 8, p378-383. Also, "hsa-miR-5010-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-5010" (miRBase Accession No. MI0017878, SEQ ID NO: 281).
[0109] As used herein, the terms "hsa-miR-6087 gene" or "hsa-miR-6087" include the hsa-miR-6087 gene (miRBase Accession No. MIMAT0023712) described in SEQ ID NO: 32, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Yoo JK et al., 2012, Stem Cells Dev, 21, p2049-2057. Also, "hsa-miR-6087" is known to have a hairpin-like structure as its precursor, "hsa-mir-6087" (miRBase Accession No. MI0020364, SEQ ID NO: 282).
[0110] As used herein, the terms "hsa-miR-6765-5p gene" or "hsa-miR-6765-5p" include the hsa-miR-6765-5p gene (miRBase Accession No. MIMAT0027430) described in SEQ ID NO: 33, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6765-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 283).
[0111] As used herein, the terms "hsa-miR-6732-5p gene" or "hsa-miR-6732-5p" include the hsa-miR-6732-5p gene (miRBase Accession No. MIMAT0027365) described in SEQ ID NO: 34, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6732-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6732" (miRBase Accession No. MI0022577, SEQ ID NO: 284).
[0112] As used herein, the terms "hsa-miR-6787-5p gene" or "hsa-miR-6787-5p" include the hsa-miR-6787-5p gene (miRBase Accession No. MIMAT0027474) described in SEQ ID NO: 35, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6787-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6787" (miRBase Accession No. MI0022632, SEQ ID NO: 285).
[0113] As used herein, the term "hsa-miR-6737-5p gene" or "hsa-miR-6737-5p" includes the hsa-miR-6737-5p gene described in SEQ ID NO: 36 (miRBase Accession No. MIMAT0027375), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6737-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6737" (miRBase Accession No. MI0022582, SEQ ID NO: 286).
[0114] As used herein, the term "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" includes the hsa-miR-128-2-5p gene described in SEQ ID NO: 37 (miRBase Accession No. MIMAT0031095), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, 12, p735-739. Also, "hsa-miR-128-2-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-128-2" (miRBase Accession No. MI0000727, SEQ ID NO: 287).
[0115] As used herein, the terms "hsa-miR-4270 gene" or "hsa-miR-4270" include the hsa-miR-4270 gene (miRBase Accession No. MIMAT0016900) described in SEQ ID NO: 38, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4270" is known to have a hairpin-like structure as its precursor, "hsa-mir-4270" (miRBase Accession No. MI0015878, SEQ ID NO: 288).
[0116] As used herein, the terms "hsa-miR-6861-5p gene" or "hsa-miR-6861-5p" include the hsa-miR-6861-5p gene (miRBase Accession No. MIMAT0027623) described in SEQ ID NO: 39, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6861-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6861" (miRBase Accession No. MI0022708, SEQ ID NO: 289).
[0117] As used herein, the terms "hsa-miR-6756-5p gene" or "hsa-miR-6756-5p" include the hsa-miR-6756-5p gene (miRBase Accession No. MIMAT0027412) described in SEQ ID NO: 40, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6756-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6756" (miRBase Accession No. MI0022601, SEQ ID NO: 290).
[0118] As used herein, the terms "hsa-miR-1229-5p gene" or "hsa-miR-1229-5p" include the hsa-miR-1229-5p gene (miRBase Accession No. MIMAT0022942) described in SEQ ID NO: 41, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336. Also, "hsa-miR-1229-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1229" (miRBase Accession No. MI0006319, SEQ ID NO: 291).
[0119] As used herein, the terms "hsa-miR-6891-5p gene" or "hsa-miR-6891-5p" include the hsa-miR-6891-5p gene (miRBase Accession No. MIMAT0027682) described in SEQ ID NO: 42, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6891-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6891" (miRBase Accession No. MI0022738, SEQ ID NO: 292).
[0120] As used herein, the terms "hsa-miR-6848-5p gene" or "hsa-miR-6848-5p" include the hsa-miR-6848-5p gene (miRBase Accession No. MIMAT0027596) described in SEQ ID NO: 43, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6848-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6848" (miRBase Accession No. MI0022694, SEQ ID NO: 293).
[0121] As used herein, the term "hsa-miR-1237-5p gene" or "hsa-miR-1237-5p" includes the hsa-miR-1237-5p gene (miRBase Accession No. MIMAT0022946) described in SEQ ID NO: 44, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336. Also, "hsa-miR-1237-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1237" (miRBase Accession No. MI0006327, SEQ ID NO: 294).
[0122] As used herein, the term "hsa-miR-30c-1-3p gene" or "hsa-miR-30c-1-3p" includes the hsa-miR-30c-1-3p gene (miRBase Accession No. MIMAT0004674) described in SEQ ID NO: 45, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, 12, p735-739. Also, "hsa-miR-30c-1-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-30c-1" (miRBase Accession No. MI0000736, SEQ ID NO: 295).
[0123] As used herein, the term "hsa-miR-1233-5p gene" or "hsa-miR-1233-5p" includes the hsa-miR-1233-5p gene described in SEQ ID NO: 46 (miRBase Accession No. MIMAT0022943), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336. Also, "hsa-miR-1233-5p" is known to have "hsa-mir-1233-1, hsa-mir-1233-2" (miRBase Accession No. MI0006323, MI0015973, SEQ ID NOs: 296, 297) with a hairpin-like structure as its precursor.
[0124] As used herein, the term "hsa-miR-211-3p gene" or "hsa-miR-211-3p" includes the hsa-miR-211-3p gene described in SEQ ID NO: 47 (miRBase Accession No. MIMAT0022694), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lim LP et al., 2003, Science, 299, p1540. Also, "hsa-miR-211-3p" is known to have "hsa-mir-211" (miRBase Accession No. MI0000287, SEQ ID NO: 298) with a hairpin-like structure as its precursor.
[0125] As used herein, the terms "hsa-miR-4758-5p gene" or "hsa-miR-4758-5p" include the hsa-miR-4758-5p gene described in SEQ ID NO: 48 (miRBase Accession No. MIMAT0019903), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4758-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4758" (miRBase Accession No. MI0017399, SEQ ID NO: 299).
[0126] As used herein, the terms "hsa-miR-614 gene" or "hsa-miR-614" include the hsa-miR-614 gene described in SEQ ID NO: 49 (miRBase Accession No. MIMAT0003282), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-614" is known to have a hairpin-like structure as its precursor, "hsa-mir-614" (miRBase Accession No. MI0003627, SEQ ID NO: 300).
[0127] As used herein, the terms "hsa-miR-6746-5p gene" or "hsa-miR-6746-5p" include the hsa-miR-6746-5p gene (miRBase Accession No. MIMAT0027392) described in SEQ ID NO: 50, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6746-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6746" (miRBase Accession No. MI0022591, SEQ ID NO: 301).
[0128] As used herein, the terms "hsa-miR-1915-5p gene" or "hsa-miR-1915-5p" include the hsa-miR-1915-5p gene (miRBase Accession No. MIMAT0007891) described in SEQ ID NO: 51, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, 26, p2496-2505. Also, "hsa-miR-1915-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 302).
[0129] As used herein, the terms "hsa-miR-4688 gene" or "hsa-miR-4688" include the hsa-miR-4688 gene described in SEQ ID NO: 52 (miRBase Accession No. MIMAT0019777), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4688" is known to have a hairpin-like structure as its precursor, "hsa-mir-4688" (miRBase Accession No. MI0017321, SEQ ID NO: 303).
[0130] As used herein, the terms "hsa-miR-3917 gene" or "hsa-miR-3917" include the hsa-miR-3917 gene described in SEQ ID NO: 53 (miRBase Accession No. MIMAT0018191), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, 5, e9637. Also, "hsa-miR-3917" is known to have a hairpin-like structure as its precursor, "hsa-mir-3917" (miRBase Accession No. MI0016423, SEQ ID NO: 304).
[0131] As used herein, the terms "hsa-miR-5787 gene" or "hsa-miR-5787" include the hsa-miR-5787 gene described in SEQ ID NO: 54 (miRBase Accession No. MIMAT0023252), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Yoo H et al., 2011, Biochem Biophys Res Commun, 415, p567-572. Also, "hsa-miR-5787" is known to have a hairpin-like structure as its precursor, "hsa-mir-5787" (miRBase Accession No. MI0019797, SEQ ID NO: 305).
[0132] As used herein, the terms "hsa-miR-4632-5p gene" or "hsa-miR-4632-5p" include the hsa-miR-4632-5p gene (miRBase Accession No. MIMAT0022977) described in SEQ ID NO: 55, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4632-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4632" (miRBase Accession No. MI0017259, SEQ ID NO: 306).
[0133] As used herein, the terms "hsa-miR-6126 gene" or "hsa-miR-6126" include the hsa-miR-6126 gene (miRBase Accession No. MIMAT0024599) described in SEQ ID NO: 56, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Smith JL et al., 2012, J Virol, 86, p5278-5287. Also, "hsa-miR-6126" is known to have a hairpin-like structure as its precursor, "hsa-mir-6126" (miRBase Accession No. MI0021260, SEQ ID NO: 307).
[0134] As used herein, the terms "hsa-miR-135a-3p gene" or "hsa-miR-135a-3p" include the hsa-miR-135a-3p gene described in SEQ ID NO: 57 (miRBase Accession No. MIMAT0004595), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, 12, p735-739. Also, "hsa-miR-135a-3p" is known to have "hsa-mir-135a-1" (miRBase Accession No. MI0000452, SEQ ID NO: 308) which forms a hairpin-like structure as its precursor.
[0135] As used herein, the terms "hsa-miR-8063 gene" or "hsa-miR-8063" include the hsa-miR-8063 gene described in SEQ ID NO: 58 (miRBase Accession No. MIMAT0030990), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Wang HJ et al., 2013, Shock, 39, p480-487. Also, "hsa-miR-8063" is known to have "hsa-mir-8063" (miRBase Accession No. MI0025899, SEQ ID NO: 309) which forms a hairpin-like structure as its precursor.
[0136] As used herein, the terms "hsa-miR-5698 gene" or "hsa-miR-5698" include the hsa-miR-5698 gene described in SEQ ID NO: 59 (miRBase Accession No. MIMAT0022491), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Watahiki A et al., 2011, PLoS One, 6, e24950. Also, "hsa-miR-5698" is known to have "hsa-mir-5698" (miRBase Accession No. MI0019305, SEQ ID NO: 310) which forms a hairpin-like structure as its precursor.
[0137] As used herein, the terms "hsa-miR-6089 gene" or "hsa-miR-6089" include the hsa-miR-6089 gene (miRBase Accession No. MIMAT0023714) described in SEQ ID NO: 60, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, 21, p2049-2057. Also, "hsa-miR-6089" is known to have "hsa-mir-6089-1, hsa-mir-6089-2" (miRBase Accession No. MI0020366, MI0023563, SEQ ID NOs: 311, 312) with a hairpin-like structure as its precursor.
[0138] As used herein, the terms "hsa-miR-498 gene" or "hsa-miR-498" include the hsa-miR-498 gene (miRBase Accession No. MIMAT0002824) described in SEQ ID NO: 61, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Bentwich I et al., 2005, Nat Genet, 37, p766-770. Also, "hsa-miR-498" is known to have "hsa-mir-498" (miRBase Accession No. MI0003142, SEQ ID NO: 313) with a hairpin-like structure as its precursor.
[0139] As used herein, the term "hsa-miR-296-3p gene" or "hsa-miR-296-3p" includes the hsa-miR-296-3p gene (miRBase Accession No. MIMAT0004679) described in SEQ ID NO: 62, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Houbaviy HB et al., 2003, Dev Cell, Vol. 5, p351-358. Also, "hsa-miR-296-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-296" (miRBase Accession No. MI0000747, SEQ ID NO: 314).
[0140] As used herein, the term "hsa-miR-4419b gene" or "hsa-miR-4419b" includes the hsa-miR-4419b gene (miRBase Accession No. MIMAT0019034) described in SEQ ID NO: 63, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-miR-4419b" is known to have a hairpin-like structure as its precursor, "hsa-mir-4419b" (miRBase Accession No. MI0016861, SEQ ID NO: 315).
[0141] As used herein, the term "hsa-miR-6802-5p gene" or "hsa-miR-6802-5p" includes the hsa-miR-6802-5p gene described in SEQ ID NO: 64 (miRBase Accession No. MIMAT0027504), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6802-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6802" (miRBase Accession No. MI0022647, SEQ ID NO: 316).
[0142] As used herein, the term "hsa-miR-6829-5p gene" or "hsa-miR-6829-5p" includes the hsa-miR-6829-5p gene described in SEQ ID NO: 65 (miRBase Accession No. MIMAT0027558), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6829-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6829" (miRBase Accession No. MI0022674, SEQ ID NO: 317).
[0143] As used herein, the term "hsa-miR-6803-5p gene" or "hsa-miR-6803-5p" includes the hsa-miR-6803-5p gene (miRBase Accession No. MIMAT0027506) described in SEQ ID NO: 66, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6803-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6803" (miRBase Accession No. MI0022648, SEQ ID NO: 318).
[0144] As used herein, the term "hsa-miR-1199-5p gene" or "hsa-miR-1199-5p" includes the hsa-miR-1199-5p gene (miRBase Accession No. MIMAT0031119) described in SEQ ID NO: 67, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Salvi A et al., 2013, Int J Oncol, 42, p391-402. Also, "hsa-miR-1199-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1199" (miRBase Accession No. MI0020340, SEQ ID NO: 319).
[0145] As used herein, the terms "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" include the hsa-miR-6840-3p gene described in SEQ ID NO: 68 (miRBase Accession No. MIMAT0027583), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6840-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6840" (miRBase Accession No. MI0022686, SEQ ID NO: 320).
[0146] As used herein, the terms "hsa-miR-6752-5p gene" or "hsa-miR-6752-5p" include the hsa-miR-6752-5p gene described in SEQ ID NO: 69 (miRBase Accession No. MIMAT0027404), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6752-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6752" (miRBase Accession No. MI0022597, SEQ ID NO: 321).
[0147] As used herein, the terms "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" include the hsa-miR-6798-5p gene described in SEQ ID NO: 70 (miRBase Accession No. MIMAT0027496), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6798-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6798" (miRBase Accession No. MI0022643, SEQ ID NO: 322).
[0148] As used herein, the terms "hsa-miR-6131 gene" or "hsa-miR-6131" include the hsa-miR-6131 gene described in SEQ ID NO: 71 (miRBase Accession No. MIMAT0024615), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol, 4, p552-564. Also, "hsa-miR-6131" is known to have a hairpin-like structure as its precursor, "hsa-mir-6131" (miRBase Accession No. MI0021276, SEQ ID NO: 323).
[0149] As used herein, the terms "hsa-miR-4667-5p gene" or "hsa-miR-4667-5p" include the hsa-miR-4667-5p gene described in SEQ ID NO: 72 (miRBase Accession No. MIMAT0019743), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78 - 86. Also, "hsa-miR-4667-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4667" (miRBase Accession No. MI0017297, SEQ ID NO: 324).
[0150] As used herein, the terms "hsa-miR-6510-5p gene" or "hsa-miR-6510-5p" include the hsa-miR-6510-5p gene described in SEQ ID NO: 73 (miRBase Accession No. MIMAT0025476), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet, 20, p4025 - 4040. Also, "hsa-miR-6510-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6510" (miRBase Accession No. MI0022222, SEQ ID NO: 325).
[0151] As used herein, the term "hsa-miR-4690-5p gene" or "hsa-miR-4690-5p" includes the hsa-miR-4690-5p gene described in SEQ ID NO: 74 (miRBase Accession No. MIMAT0019779), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4690-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4690" (miRBase Accession No. MI0017323, SEQ ID NO: 326).
[0152] As used herein, the term "hsa-miR-920 gene" or "hsa-miR-920" includes the hsa-miR-920 gene described in SEQ ID NO: 75 (miRBase Accession No. MIMAT0004970), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Novotny GW et al., 2007, Int J Androl, 30, p316-326. Also, "hsa-miR-920" is known to have a hairpin-like structure as its precursor, "hsa-mir-920" (miRBase Accession No. MI0005712, SEQ ID NO: 327).
[0153] As used herein, the terms "hsa-miR-23b-3p gene" or "hsa-miR-23b-3p" include the hsa-miR-23b-3p gene (miRBase Accession No. MIMAT0000418) described in SEQ ID NO: 76, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739. Also, "hsa-miR-23b-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-23b" (miRBase Accession No. MI0000439, SEQ ID NO: 328).
[0154] As used herein, the terms "hsa-miR-4448 gene" or "hsa-miR-4448" include the hsa-miR-4448 gene (miRBase Accession No. MIMAT0018967) described in SEQ ID NO: 77, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-miR-4448" is known to have a hairpin-like structure as its precursor, "hsa-mir-4448" (miRBase Accession No. MI0016791, SEQ ID NO: 329).
[0155] As used herein, the terms "hsa-miR-2110 gene" or "hsa-miR-2110" include the hsa-miR-2110 gene (miRBase Accession No. MIMAT0010133) described in SEQ ID NO: 78, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Zhu JY et al., 2009, J Virol, Vol. 83, p3333-3341. Also, "hsa-miR-2110" is known to have a hairpin-like structure as its precursor, "hsa-mir-2110" (miRBase Accession No. MI0010629, SEQ ID NO: 330).
[0156] As used herein, the terms "hsa-miR-4706 gene" or "hsa-miR-4706" include the hsa-miR-4706 gene described in SEQ ID NO: 79 (miRBase Accession No. MIMAT0019806), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4706" is known to have a hairpin-like structure as its precursor, "hsa-mir-4706" (miRBase Accession No. MI0017339, SEQ ID NO: 331).
[0157] As used herein, the terms "hsa-miR-7845-5p gene" or "hsa-miR-7845-5p" include the hsa-miR-7845-5p gene described in SEQ ID NO: 80 (miRBase Accession No. MIMAT0030420), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ple H et al., 2012, PLoS One, 7, e50746. Also, "hsa-miR-7845-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7845" (miRBase Accession No. MI0025515, SEQ ID NO: 332).
[0158] As used herein, the terms "hsa-miR-6808-5p gene" or "hsa-miR-6808-5p" include the hsa-miR-6808-5p gene (miRBase Accession No. MIMAT0027516) described in SEQ ID NO: 81, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6808-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6808" (miRBase Accession No. MI0022653, SEQ ID NO: 333).
[0159] As used herein, the terms "hsa-miR-4447 gene" or "hsa-miR-4447" include the hsa-miR-4447 gene (miRBase Accession No. MIMAT0018966) described in SEQ ID NO: 82, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4447" is known to have a hairpin-like structure as its precursor, "hsa-mir-4447" (miRBase Accession No. MI0016790, SEQ ID NO: 334).
[0160] As used herein, the terms "hsa-miR-6869-5p gene" or "hsa-miR-6869-5p" include the hsa-miR-6869-5p gene (miRBase Accession No. MIMAT0027638) described in SEQ ID NO: 83, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6869-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6869" (miRBase Accession No. MI0022716, SEQ ID NO: 335).
[0161] As used herein, the terms "hsa-miR-1908-5p gene" or "hsa-miR-1908-5p" include the hsa-miR-1908-5p gene (miRBase Accession No. MIMAT0007881) described in SEQ ID NO: 84, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, 26, p2496-2505. Also, "hsa-miR-1908-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1908" (miRBase Accession No. MI0008329, SEQ ID NO: 336).
[0162] As used herein, the term "hsa-miR-6729-5p gene" or "hsa-miR-6729-5p" includes the hsa-miR-6729-5p gene (miRBase Accession No. MIMAT0027359) described in SEQ ID NO: 85, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6729-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6729" (miRBase Accession No. MI0022574, SEQ ID NO: 337).
[0163] As used herein, the term "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" includes the hsa-miR-5195-3p gene (miRBase Accession No. MIMAT0021127) described in SEQ ID NO: 86, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Schotte D et al., 2011, Leukemia, 25, p1389-1399. Also, "hsa-miR-5195-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-5195" (miRBase Accession No. MI0018174, SEQ ID NO: 338).
[0164] As used herein, the terms "hsa-miR-638 gene" or "hsa-miR-638" include the hsa-miR-638 gene described in SEQ ID NO: 87 (miRBase Accession No. MIMAT0003308), as well as homologs or orthologs in other species. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-638" is known to have a precursor "hsa-mir-638" (miRBase Accession No. MI0003653, SEQ ID NO: 339) that forms a hairpin-like structure.
[0165] As used herein, the terms "hsa-miR-6125 gene" or "hsa-miR-6125" include the hsa-miR-6125 gene described in SEQ ID NO: 88 (miRBase Accession No. MIMAT0024598), as well as homologs or orthologs in other species. The gene can be obtained by the method described in Smith JL et al., 2012, J Virol, 86, p5278-5287. Also, "hsa-miR-6125" is known to have a precursor "hsa-mir-6125" (miRBase Accession No. MI0021259, SEQ ID NO: 340) that forms a hairpin-like structure.
[0166] As used herein, the terms "hsa-miR-3178 gene" or "hsa-miR-3178" include the hsa-miR-3178 gene described in SEQ ID NO: 89 (miRBase Accession No. MIMAT0015055), as well as homologs or orthologs in other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3178" is known to have a precursor "hsa-mir-3178" (miRBase Accession No. MI0014212, SEQ ID NO: 341) that forms a hairpin-like structure.
[0167] As used herein, the terms "hsa-miR-3196 gene" or "hsa-miR-3196" include the hsa-miR-3196 gene described in SEQ ID NO: 90 (miRBase Accession No. MIMAT0015080), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3196" is known to have a hairpin-like structure as its precursor, "hsa-mir-3196" (miRBase Accession No. MI0014241, SEQ ID NO: 342).
[0168] As used herein, the terms "hsa-miR-8069 gene" or "hsa-miR-8069" include the hsa-miR-8069 gene described in SEQ ID NO: 91 (miRBase Accession No. MIMAT0030996), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Wang HJ et al., 2013, Shock, 39, p480-487. Also, "hsa-miR-8069" is known to have a hairpin-like structure as its precursor, "hsa-mir-8069-1, hsa-mir-8069-2" (miRBase Accession No. MI0025905, MI0031519, SEQ ID NO: 343, 344).
[0169] As used herein, the term "hsa-miR-4723-5p gene" or "hsa-miR-4723-5p" includes the hsa-miR-4723-5p gene (miRBase Accession No. MIMAT0019838) described in SEQ ID NO: 92, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4723-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4723" (miRBase Accession No. MI0017359, SEQ ID NO: 345).
[0170] As used herein, the term "hsa-miR-4746-3p gene" or "hsa-miR-4746-3p" includes the hsa-miR-4746-3p gene (miRBase Accession No. MIMAT0019881) described in SEQ ID NO: 93, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4746-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4746" (miRBase Accession No. MI0017385, SEQ ID NO: 346).
[0171] As used herein, the terms "hsa-miR-4689 gene" or "hsa-miR-4689" include the hsa-miR-4689 gene (miRBase Accession No. MIMAT0019778) described in SEQ ID NO: 94, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4689" is known to have a hairpin-like structure as its precursor, "hsa-mir-4689" (miRBase Accession No. MI0017322, SEQ ID NO: 347).
[0172] As used herein, the terms "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" include the hsa-miR-6816-5p gene (miRBase Accession No. MIMAT0027532) described in SEQ ID NO: 95, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6816-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6816" (miRBase Accession No. MI0022661, SEQ ID NO: 348).
[0173] As used herein, the term "hsa-miR-6757-5p gene" or "hsa-miR-6757-5p" includes the hsa-miR-6757-5p gene (miRBase Accession No. MIMAT0027414) described in SEQ ID NO: 96, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6757-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6757" (miRBase Accession No. MI0022602, SEQ ID NO: 349).
[0174] As used herein, the term "hsa-miR-7109-5p gene" or "hsa-miR-7109-5p" includes the hsa-miR-7109-5p gene (miRBase Accession No. MIMAT0028115) described in SEQ ID NO: 97, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-7109-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7109" (miRBase Accession No. MI0022960, SEQ ID NO: 350).
[0175] As used herein, the terms "hsa-miR-6724-5p gene" or "hsa-miR-6724-5p" include the hsa-miR-6724-5p gene (miRBase Accession No. MIMAT0025856) described in SEQ ID NO: 98, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Also, "hsa-miR-6724-5p" is known to have "hsa-mir-6724-1, hsa-mir-6724-2, hsa-mir-6724-3, hsa-mir-6724-4" (miRBase Accession Nos. MI0022559, MI0031516, MI0031517, MI0031518, SEQ ID NOs: 351, 352, 353, 354) that form a hairpin-like structure as its precursor.
[0176] As used herein, the terms "hsa-miR-1225-3p gene" or "hsa-miR-1225-3p" include the hsa-miR-1225-3p gene (miRBase Accession No. MIMAT0005573) described in SEQ ID NO: 99, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Also, "hsa-miR-1225-3p" is known to have "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 355) that forms a hairpin-like structure as its precursor.
[0177] As used herein, the term "hsa-miR-6875-5p gene" or "hsa-miR-6875-5p" includes the hsa-miR-6875-5p gene (miRBase Accession No. MIMAT0027650) described in SEQ ID NO: 100, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6875-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6875" (miRBase Accession No. MI0022722, SEQ ID NO: 356).
[0178] As used herein, the term "hsa-miR-7108-5p gene" or "hsa-miR-7108-5p" includes the hsa-miR-7108-5p gene (miRBase Accession No. MIMAT0028113) described in SEQ ID NO: 101, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-7108-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7108" (miRBase Accession No. MI0022959, SEQ ID NO: 357).
[0179] As used herein, the terms "hsa-miR-4508 gene" or "hsa-miR-4508" include the hsa-miR-4508 gene (miRBase Accession No. MIMAT0019045) described in SEQ ID NO: 102, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4508" is known to have a hairpin-like structure as its precursor, "hsa-mir-4508" (miRBase Accession No. MI0016872, SEQ ID NO: 358).
[0180] As used herein, the terms "hsa-miR-6085 gene" or "hsa-miR-6085" include the hsa-miR-6085 gene (miRBase Accession No. MIMAT0023710) described in SEQ ID NO: 103, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Voellenkle C et al., 2012, RNA, 18, p472-484. Also, "hsa-miR-6085" is known to have a hairpin-like structure as its precursor, "hsa-mir-6085" (miRBase Accession No. MI0020362, SEQ ID NO: 359).
[0181] As used herein, the terms "hsa-miR-6779-5p gene" or "hsa-miR-6779-5p" include the hsa-miR-6779-5p gene (miRBase Accession No. MIMAT0027458) described in SEQ ID NO: 104, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6779-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6779" (miRBase Accession No. MI0022624, SEQ ID NO: 360).
[0182] As used herein, the terms "hsa-miR-642a-3p gene" or "hsa-miR-642a-3p" include the hsa-miR-642a-3p gene described in SEQ ID NO: 105 (miRBase Accession No. MIMAT0020924), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-642a-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-642a" (miRBase Accession No. MI0003657, SEQ ID NO: 361).
[0183] As used herein, the terms "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" include the hsa-miR-4695-5p gene described in SEQ ID NO: 106 (miRBase Accession No. MIMAT0019788), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4695-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4695" (miRBase Accession No. MI0017328, SEQ ID NO: 362).
[0184] As used herein, the terms "hsa-miR-7847-3p gene" or "hsa-miR-7847-3p" include the hsa-miR-7847-3p gene described in SEQ ID NO: 107 (miRBase Accession No. MIMAT0030422), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ple H et al., 2012, PLoS One, 7, e50746. Also, "hsa-miR-7847-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7847" (miRBase Accession No. MI0025517, SEQ ID NO: 363).
[0185] As used herein, the terms "hsa-miR-3197 gene" or "hsa-miR-3197" include the hsa-miR-3197 gene described in SEQ ID NO: 108 (miRBase Accession No. MIMAT0015082), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3197" is known to have a hairpin-like structure as its precursor, "hsa-mir-3197" (miRBase Accession No. MI0014245, SEQ ID NO: 364).
[0186] As used herein, the terms "hsa-miR-6769b-5p gene" or "hsa-miR-6769b-5p" include the hsa-miR-6769b-5p gene (miRBase Accession No. MIMAT0027620) described in SEQ ID NO: 109, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6769b-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6769b" (miRBase Accession No. MI0022706, SEQ ID NO: 365).
[0187] As used herein, the terms "hsa-miR-7641 gene" or "hsa-miR-7641" include the hsa-miR-7641 gene (miRBase Accession No. MIMAT0029782) described in SEQ ID NO: 110, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Yoo JK et al., 2013, Arch Pharm Res, 36, p353-358. Also, "hsa-miR-7641" is known to have a hairpin-like structure as its precursor, "hsa-mir-7641-1, hsa-mir-7641-2" (miRBase Accession No. MI0024975, MI0024976, SEQ ID NO: 366, 367).
[0188] As used herein, the term "hsa-miR-187-5p gene" or "hsa-miR-187-5p" includes the hsa-miR-187-5p gene (miRBase Accession No. MIMAT0004561) described in SEQ ID NO: 111, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Lim LP et al., Science, Vol. 299, p1540, 2003. Also, "hsa-miR-187-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-187" (miRBase Accession No. MI0000274, SEQ ID NO: 368).
[0189] As used herein, the term "hsa-miR-3185 gene" or "hsa-miR-3185" includes the hsa-miR-3185 gene (miRBase Accession No. MIMAT0015065) described in SEQ ID NO: 112, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Stark MS et al., PLoS One, Vol. 5, e9685, 2010. Also, "hsa-miR-3185" is known to have a hairpin-like structure as its precursor, "hsa-mir-3185" (miRBase Accession No. MI0014227, SEQ ID NO: 369).
[0190] As used herein, the term "hsa-miR-2861 gene" or "hsa-miR-2861" includes the hsa-miR-2861 gene (miRBase Accession No. MIMAT0013802) described in SEQ ID NO: 113, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Li H et al., J Clin Invest, Vol. 119, p3666 - 3677, 2009. Also, "hsa-miR-2861" is known to have a hairpin-like structure as its precursor, "hsa-mir-2861" (miRBase Accession No. MI0013006, SEQ ID NO: 370).
[0191] As used herein, the term "hsa-miR-3940-5p gene" or "hsa-miR-3940-5p" includes the hsa-miR-3940-5p gene described in SEQ ID NO: 114 (miRBase Accession No. MIMAT0019229), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Also, "hsa-miR-3940-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3940" (miRBase Accession No. MI0016597, SEQ ID NO: 371).
[0192] As used herein, the term "hsa-miR-1203 gene" or "hsa-miR-1203" includes the hsa-miR-1203 gene described in SEQ ID NO: 115 (miRBase Accession No. MIMAT0005866), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Marton S et al., 2008, Leukemia, Vol. 22, p330-338. Also, "hsa-miR-1203" is known to have a hairpin-like structure as its precursor, "hsa-mir-1203" (miRBase Accession No. MI0006335, SEQ ID NO: 372).
[0193] As used herein, the term "hsa-miR-615-5p gene" or "hsa-miR-615-5p" includes the hsa-miR-615-5p gene described in SEQ ID NO: 116 (miRBase Accession No. MIMAT0004804), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-615-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-615" (miRBase Accession No. MI0003628, SEQ ID NO: 373).
[0194] As used herein, the term "hsa-miR-4787-5p gene" or "hsa-miR-4787-5p" includes the hsa-miR-4787-5p gene described in SEQ ID NO: 117 (miRBase Accession No. MIMAT0019956), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4787-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4787" (miRBase Accession No. MI0017434, SEQ ID NO: 374).
[0195] As used herein, the terms "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" include the hsa-miR-1343-3p gene described in SEQ ID NO: 118 (miRBase Accession No. MIMAT0019776), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-1343-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 375).
[0196] As used herein, the terms "hsa-miR-6813-5p gene" or "hsa-miR-6813-5p" include the hsa-miR-6813-5p gene described in SEQ ID NO: 119 (miRBase Accession No. MIMAT0027526), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6813-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6813" (miRBase Accession No. MI0022658, SEQ ID NO: 376).
[0197] As used herein, the term "hsa-miR-1225-5p gene" or "hsa-miR-1225-5p" includes the hsa-miR-1225-5p gene described in SEQ ID NO: 120 (miRBase Accession No. MIMAT0005572), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, p328-336. Also, "hsa-miR-1225-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 377).
[0198] As used herein, the term "hsa-miR-602 gene" or "hsa-miR-602" includes the hsa-miR-602 gene described in SEQ ID NO: 121 (miRBase Accession No. MIMAT0003270), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, Vol. 103, p3687-3692. Also, "hsa-miR-602" is known to have a hairpin-like structure as its precursor, "hsa-mir-602" (miRBase Accession No. MI0003615, SEQ ID NO: 378).
[0199] As used herein, the term "hsa-miR-4488 gene" or "hsa-miR-4488" includes the hsa-miR-4488 gene described in SEQ ID NO: 122 (miRBase Accession No. MIMAT0019022), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, pp. e118-e127. Also, "hsa-miR-4488" is known to have a hairpin-like structure as its precursor, "hsa-mir-4488" (miRBase Accession No. MI0016849, SEQ ID NO: 379).
[0200] As used herein, the term "hsa-miR-125a-3p gene" or "hsa-miR-125a-3p" includes the hsa-miR-125a-3p gene described in SEQ ID NO: 123 (miRBase Accession No. MIMAT0004602), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Also, "hsa-miR-125a-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-125a" (miRBase Accession No. MI0000469, SEQ ID NO: 380).
[0201] As used herein, the terms "hsa-miR-5100 gene" or "hsa-miR-5100" include the hsa-miR-5100 gene described in SEQ ID NO: 124 (miRBase Accession No. MIMAT0022259), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Tandon M et al., 2012, Oral Dis, 18, p127-131. Also, "hsa-miR-5100" is known to have a hairpin-like structure as its precursor, "hsa-mir-5100" (miRBase Accession No. MI0019116, SEQ ID NO: 381).
[0202] As used herein, the terms "hsa-miR-4294 gene" or "hsa-miR-4294" include the hsa-miR-4294 gene described in SEQ ID NO: 125 (miRBase Accession No. MIMAT0016849), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4294" is known to have a hairpin-like structure as its precursor, "hsa-mir-4294" (miRBase Accession No. MI0015827, SEQ ID NO: 382).
[0203] As used herein, the terms "hsa-miR-1231 gene" or "hsa-miR-1231" include the hsa-miR-1231 gene described in SEQ ID NO: 126 (miRBase Accession No. MIMAT0005586), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336. Also, "hsa-miR-1231" is known to have a hairpin-like structure as its precursor, "hsa-mir-1231" (miRBase Accession No. MI0006321, SEQ ID NO: 383).
[0204] As used herein, the term "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" includes the hsa-miR-6765-3p gene described in SEQ ID NO: 127 (miRBase Accession No. MIMAT0027431), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6765-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 384).
[0205] As used herein, the term "hsa-miR-4442 gene" or "hsa-miR-4442" includes the hsa-miR-4442 gene described in SEQ ID NO: 128 (miRBase Accession No. MIMAT0018960), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4442" is known to have a hairpin-like structure as its precursor, "hsa-mir-4442" (miRBase Accession No. MI0016785, SEQ ID NO: 385).
[0206] As used herein, the terms "hsa-miR-718 gene" or "hsa-miR-718" include the hsa-miR-718 gene described in SEQ ID NO: 129 (miRBase Accession No. MIMAT0012735), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Artzi S et al., 2008, BMC Bioinformatics, 9, p39. Also, "hsa-miR-718" is known to have a hairpin-like structure as its precursor, "hsa-mir-718" (miRBase Accession No. MI0012489, SEQ ID NO: 386).
[0207] As used herein, the terms "hsa-miR-6780b-5p gene" or "hsa-miR-6780b-5p" include the hsa-miR-6780b-5p gene described in SEQ ID NO: 130 (miRBase Accession No. MIMAT0027572), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6780b-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6780b" (miRBase Accession No. MI0022681, SEQ ID NO: 387).
[0208] As used herein, the term "hsa-miR-6090 gene" or "hsa-miR-6090" includes the hsa-miR-6090 gene described in SEQ ID NO: 131 (miRBase Accession No. MIMAT0023715), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, 21, p2049-2057. Also, "hsa-miR-6090" is known to have a hairpin-like structure as its precursor, "hsa-mir-6090" (miRBase Accession No. MI0020367, SEQ ID NO: 388).
[0209] As used herein, the term "hsa-miR-6845-5p gene" or "hsa-miR-6845-5p" includes the hsa-miR-6845-5p gene described in SEQ ID NO: 132 (miRBase Accession No. MIMAT0027590), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6845-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6845" (miRBase Accession No. MI0022691, SEQ ID NO: 389).
[0210] As used herein, the term "hsa-miR-4741 gene" or "hsa-miR-4741" includes the hsa-miR-4741 gene described in SEQ ID NO: 133 (miRBase Accession No. MIMAT0019871), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4741" is known to have a hairpin-like structure as its precursor, "hsa-mir-4741" (miRBase Accession No. MI0017379, SEQ ID NO: 390).
[0211] As used herein, the term "hsa-miR-4467 gene" or "hsa-miR-4467" includes the hsa-miR-4467 gene described in SEQ ID NO: 134 (miRBase Accession No. MIMAT0018994), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4467" is known to have a hairpin-like structure as its precursor, "hsa-mir-4467" (miRBase Accession No. MI0016818, SEQ ID NO: 391).
[0212] As used herein, the term "hsa-miR-4707-5p gene" or "hsa-miR-4707-5p" includes the hsa-miR-4707-5p gene described in SEQ ID NO: 135 (miRBase Accession No. MIMAT0019807), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4707-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 392).
[0213] As used herein, the terms "hsa-miR-4271 gene" or "hsa-miR-4271" include the hsa-miR-4271 gene described in SEQ ID NO: 136 (miRBase Accession No. MIMAT0016901), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Also, "hsa-miR-4271" is known to have a hairpin-like structure as its precursor, "hsa-mir-4271" (miRBase Accession No. MI0015879, SEQ ID NO: 393).
[0214] As used herein, the terms "hsa-miR-4673 gene" or "hsa-miR-4673" include the hsa-miR-4673 gene described in SEQ ID NO: 137 (miRBase Accession No. MIMAT0019755), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, p78-86. Also, "hsa-miR-4673" is known to have a hairpin-like structure as its precursor, "hsa-mir-4673" (miRBase Accession No. MI0017304, SEQ ID NO: 394).
[0215] As used herein, the terms "hsa-miR-3184-5p gene" or "hsa-miR-3184-5p" include the hsa-miR-3184-5p gene described in SEQ ID NO: 138 (miRBase Accession No. MIMAT0015064), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3184-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3184" (miRBase Accession No. MI0014226, SEQ ID NO: 395).
[0216] As used herein, the terms "hsa-miR-1469 gene" or "hsa-miR-1469" include the hsa-miR-1469 gene described in SEQ ID NO: 139 (miRBase Accession No. MIMAT0007347), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Kawaji H et al., 2008, BMC Genomics, 9, p157. Also, "hsa-miR-1469" is known to have a hairpin-like structure as its precursor, "hsa-mir-1469" (miRBase Accession No. MI0007074, SEQ ID NO: 396).
[0217] As used herein, the term "hsa-miR-4640-5p gene" or "hsa-miR-4640-5p" includes the hsa-miR-4640-5p gene (miRBase Accession No. MIMAT0019699) described in SEQ ID NO: 140, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4640-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4640" (miRBase Accession No. MI0017267, SEQ ID NO: 397).
[0218] As used herein, the term "hsa-miR-663a gene" or "hsa-miR-663a" includes the hsa-miR-663a gene (miRBase Accession No. MIMAT0003326) described in SEQ ID NO: 141, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-663a" is known to have a hairpin-like structure as its precursor, "hsa-mir-663a" (miRBase Accession No. MI0003672, SEQ ID NO: 398).
[0219] As used herein, the terms "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" include the hsa-miR-6791-5p gene described in SEQ ID NO: 142 (miRBase Accession No. MIMAT0027482), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6791-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6791" (miRBase Accession No. MI0022636, SEQ ID NO: 399).
[0220] As used herein, the terms "hsa-miR-6826-5p gene" or "hsa-miR-6826-5p" include the hsa-miR-6826-5p gene described in SEQ ID NO: 143 (miRBase Accession No. MIMAT0027552), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6826-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6826" (miRBase Accession No. MI0022671, SEQ ID NO: 400).
[0221] As used herein, the term "hsa-miR-4433b-3p gene" or "hsa-miR-4433b-3p" includes the hsa-miR-4433b-3p gene described in SEQ ID NO: 144 (miRBase Accession No. MIMAT0030414), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Ple H et al., 2012, PLoS One, 7, e50746. Also, "hsa-miR-4433b-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4433b" (miRBase Accession No. MI0025511, SEQ ID NO: 401).
[0222] As used herein, the term "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" includes the hsa-miR-1915-3p gene described in SEQ ID NO: 145 (miRBase Accession No. MIMAT0007892), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Bar M et al., 2008, Stem Cells, 26, p2496 - 2505. Also, "hsa-miR-1915-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 402).
[0223] As used herein, the terms "hsa-miR-4417 gene" or "hsa-miR-4417" include the hsa-miR-4417 gene described in SEQ ID NO: 146 (miRBase Accession No. MIMAT0018929), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, pp. e118-e127. Also, "hsa-miR-4417" is known to have a hairpin-like structure as its precursor, "hsa-mir-4417" (miRBase Accession No. MI0016753, SEQ ID NO: 403).
[0224] As used herein, the terms "hsa-miR-4449 gene" or "hsa-miR-4449" include the hsa-miR-4449 gene described in SEQ ID NO: 147 (miRBase Accession No. MIMAT0018968), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, pp. e118-e127. Also, "hsa-miR-4449" is known to have a hairpin-like structure as its precursor, "hsa-mir-4449" (miRBase Accession No. MI0016792, SEQ ID NO: 404).
[0225] As used herein, the terms "hsa-miR-4707-3p gene" or "hsa-miR-4707-3p" include the hsa-miR-4707-3p gene described in SEQ ID NO: 148 (miRBase Accession No. MIMAT0019808), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, "hsa-miR-4707-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 405).
[0226] As used herein, the terms "hsa-miR-3180-3p gene" or "hsa-miR-3180-3p" include the hsa-miR-3180-3p gene described in SEQ ID NO: 149 (miRBase Accession No. MIMAT0015058), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, 5, e9637. Also, "hsa-miR-3180-3p" is known to have "hsa-mir-3180-1, hsa-mir-3180-2, hsa-mir-3180-3" (miRBase Accession No. MI0014214, MI0014215, MI0014217, SEQ ID NOs: 406, 407, 408) with a hairpin-like structure as its precursor.
[0227] As used herein, the terms "hsa-miR-5585-3p gene" or "hsa-miR-5585-3p" include the hsa-miR-5585-3p gene described in SEQ ID NO: 150 (miRBase Accession No. MIMAT0022286), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Friedlander MR et al., 2012, Nucleic Acids Res, 40, p37-52. Also, "hsa-miR-5585-3p" is known to have "hsa-mir-5585" (miRBase Accession No. MI0019142, SEQ ID NO: 409) with a hairpin-like structure as its precursor.
[0228] As used herein, the term "hsa-miR-1268a gene" or "hsa-miR-1268a" includes the hsa-miR-1268a gene described in SEQ ID NO: 151 (miRBase Accession No. MIMAT0005922), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, 18, p610-621. Also, "hsa-miR-1268a" is known to have a hairpin-like structure as its precursor, "hsa-mir-1268a" (miRBase Accession No. MI0006405, SEQ ID NO: 410).
[0229] As used herein, the term "hsa-miR-8072 gene" or "hsa-miR-8072" includes the hsa-miR-8072 gene described in SEQ ID NO: 152 (miRBase Accession No. MIMAT0030999), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Wang HJ et al., 2013, Shock, 39, p480-487. Also, "hsa-miR-8072" is known to have a hairpin-like structure as its precursor, "hsa-mir-8072" (miRBase Accession No. MI0025908, SEQ ID NO: 411).
[0230] As used herein, the term "hsa-miR-296-5p gene" or "hsa-miR-296-5p" includes the hsa-miR-296-5p gene described in SEQ ID NO: 153 (miRBase Accession No. MIMAT0000690), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Houbaviy HB et al., 2003, Dev Cell, 5, p351-358. Also, "hsa-miR-296-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-296" (miRBase Accession No. MI0000747, SEQ ID NO: 412).
[0231] As used herein, the terms "hsa-miR-204-3p gene" or "hsa-miR-204-3p" include the hsa-miR-204-3p gene described in SEQ ID NO: 154 (miRBase Accession No. MIMAT0022693), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Lim LP et al., Science, Vol. 299, p1540, 2003. Also, "hsa-miR-204-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-204" (miRBase Accession No. MI0000284, SEQ ID NO: 413).
[0232] As used herein, the terms "hsa-miR-4454 gene" or "hsa-miR-4454" include the hsa-miR-4454 gene described in SEQ ID NO: 155 (miRBase Accession No. MIMAT0018976), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Jima DD et al., Blood, Vol. 116, e118-e127, 2010. Also, "hsa-miR-4454" is known to have a hairpin-like structure as its precursor, "hsa-mir-4454" (miRBase Accession No. MI0016800, SEQ ID NO: 414).
[0233] As used herein, the term "hsa-miR-6722-3p gene" or "hsa-miR-6722-3p" includes the hsa-miR-6722-3p gene (miRBase Accession No. MIMAT0025854) described in SEQ ID NO: 156, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, p330-335. Also, "hsa-miR-6722-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6722" (miRBase Accession No. MI0022557, SEQ ID NO: 415).
[0234] As used herein, the term "hsa-miR-1290 gene" or "hsa-miR-1290" includes the hsa-miR-1290 gene (miRBase Accession No. MIMAT0005880) described in SEQ ID NO: 157, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, Vol. 18, p610-621. Also, "hsa-miR-1290" is known to have a hairpin-like structure as its precursor, "hsa-mir-1290" (miRBase Accession No. MI0006352, SEQ ID NO: 416).
[0235] As used herein, the term "hsa-miR-3622a-5p gene" or "hsa-miR-3622a-5p" includes the hsa-miR-3622a-5p gene described in SEQ ID NO: 158 (miRBase Accession No. MIMAT0018003), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Witten D et al., 2010, BMC Biol, 8, p58. Also, "hsa-miR-3622a-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3622a" (miRBase Accession No. MI0016013, SEQ ID NO: 417).
[0236] As used herein, the term "hsa-miR-939-5p gene" or "hsa-miR-939-5p" includes the hsa-miR-939-5p gene described in SEQ ID NO: 159 (miRBase Accession No. MIMAT0004982), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Lui WO et al., 2007, Cancer Res, 67, p6031-6043. Also, "hsa-miR-939-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-939" (miRBase Accession No. MI0005761, SEQ ID NO: 418).
[0237] As used herein, the terms "hsa-miR-675-5p gene" or "hsa-miR-675-5p" include the hsa-miR-675-5p gene described in SEQ ID NO: 160 (miRBase Accession No. MIMAT0004284), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Cai X et al., 2007, RNA, Vol. 13, p313-316. Also, "hsa-miR-675-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-675" (miRBase Accession No. MI0005416, SEQ ID NO: 419).
[0238] As used herein, the terms "hsa-miR-3131 gene" or "hsa-miR-3131" include the hsa-miR-3131 gene described in SEQ ID NO: 161 (miRBase Accession No. MIMAT0014996), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-miR-3131" is known to have a hairpin-like structure as its precursor, "hsa-mir-3131" (miRBase Accession No. MI0014151, SEQ ID NO: 420).
[0239] As used herein, the terms "hsa-miR-4648 gene" or "hsa-miR-4648" include the hsa-miR-4648 gene described in SEQ ID NO: 162 (miRBase Accession No. MIMAT0019710), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, p78-86. Also, "hsa-miR-4648" is known to have a hairpin-like structure as its precursor, "hsa-mir-4648" (miRBase Accession No. MI0017275, SEQ ID NO: 421).
[0240] As used herein, the terms "hsa-miR-1268b gene" or "hsa-miR-1268b" include the hsa-miR-1268b gene (miRBase Accession No. MIMAT0018925) described in SEQ ID NO: 163, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-miR-1268b" is known to have a hairpin-like structure as its precursor, "hsa-mir-1268b" (miRBase Accession No. MI0016748, SEQ ID NO: 422).
[0241] As used herein, the terms "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" include the hsa-miR-6741-5p gene (miRBase Accession No. MIMAT0027383) described in SEQ ID NO: 164, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645. Also, "hsa-miR-6741-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6741" (miRBase Accession No. MI0022586, SEQ ID NO: 423).
[0242] As used herein, the terms "hsa-miR-6893-5p gene" or "hsa-miR-6893-5p" include the hsa-miR-6893-5p gene (miRBase Accession No. MIMAT0027686) described in SEQ ID NO: 165, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6893-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6893" (miRBase Accession No. MI0022740, SEQ ID NO: 424).
[0243] As used herein, the terms "hsa-miR-3162-5p gene" or "hsa-miR-3162-5p" include the hsa-miR-3162-5p gene (miRBase Accession No. MIMAT0015036) described in SEQ ID NO: 166, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3162-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3162" (miRBase Accession No. MI0014192, SEQ ID NO: 425).
[0244] As used herein, the terms "hsa-miR-642b-3p gene" or "hsa-miR-642b-3p" include the hsa-miR-642b-3p gene (miRBase Accession No. MIMAT0018444) described in SEQ ID NO: 167, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, 8, p58. Also, "hsa-miR-642b-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-642b" (miRBase Accession No. MI0016685, SEQ ID NO: 426).
[0245] As used herein, the terms "hsa-miR-4734 gene" or "hsa-miR-4734" include the hsa-miR-4734 gene (miRBase Accession No. MIMAT0019859) described in SEQ ID NO: 168, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4734" is known to have a hairpin-like structure as its precursor, "hsa-mir-4734" (miRBase Accession No. MI0017371, SEQ ID NO: 427).
[0246] As used herein, the term "hsa-miR-150-3p gene" or "hsa-miR-150-3p" includes the hsa-miR-150-3p gene described in SEQ ID NO: 169 (miRBase Accession No. MIMAT0004610), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739. Also, "hsa-miR-150-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-150" (miRBase Accession No. MI0000479, SEQ ID NO: 428).
[0247] As used herein, the term "hsa-miR-8089 gene" or "hsa-miR-8089" includes the hsa-miR-8089 gene described in SEQ ID NO: 170 (miRBase Accession No. MIMAT0031016), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, p480-487. Also, "hsa-miR-8089" is known to have a hairpin-like structure as its precursor, "hsa-mir-8089" (miRBase Accession No. MI0025925, SEQ ID NO: 429).
[0248] As used herein, the term "hsa-miR-6805-3p gene" or "hsa-miR-6805-3p" includes the hsa-miR-6805-3p gene described in SEQ ID NO: 171 (miRBase Accession No. MIMAT0027511), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6805-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6805" (miRBase Accession No. MI0022650, SEQ ID NO: 430).
[0249] As used herein, the term "hsa-miR-7113-3p gene" or "hsa-miR-7113-3p" includes the hsa-miR-7113-3p gene described in SEQ ID NO: 172 (miRBase Accession No. MIMAT0028124), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-7113-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7113" (miRBase Accession No. MI0022964, SEQ ID NO: 431).
[0250] As used herein, the terms "hsa-miR-6850-5p gene" or "hsa-miR-6850-5p" include the hsa-miR-6850-5p gene (miRBase Accession No. MIMAT0027600) described in SEQ ID NO: 173, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6850-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6850" (miRBase Accession No. MI0022696, SEQ ID NO: 432).
[0251] As used herein, the terms "hsa-miR-6799-5p gene" or "hsa-miR-6799-5p" include the hsa-miR-6799-5p gene (miRBase Accession No. MIMAT0027498) described in SEQ ID NO: 174, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6799-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6799" (miRBase Accession No. MI0022644, SEQ ID NO: 433).
[0252] As used herein, the term "hsa-miR-6768-5p gene" or "hsa-miR-6768-5p" includes the hsa-miR-6768-5p gene described in SEQ ID NO: 175 (miRBase Accession No. MIMAT0027436), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6768-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6768" (miRBase Accession No. MI0022613, SEQ ID NO: 434).
[0253] As used herein, the term "hsa-miR-92b-5p gene" or "hsa-miR-92b-5p" includes the hsa-miR-92b-5p gene described in SEQ ID NO: 176 (miRBase Accession No. MIMAT0004792), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-92b-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-92b" (miRBase Accession No. MI0003560, SEQ ID NO: 435).
[0254] As used herein, the term "hsa-miR-3679-5p gene" or "hsa-miR-3679-5p" includes the hsa-miR-3679-5p gene (miRBase Accession No. MIMAT0018104) described in SEQ ID NO: 177, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, 5, e9637. Also, "hsa-miR-3679-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 436).
[0255] As used herein, the term "hsa-miR-4792 gene" or "hsa-miR-4792" includes the hsa-miR-4792 gene (miRBase Accession No. MIMAT0019964) described in SEQ ID NO: 178, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4792" is known to have a hairpin-like structure as its precursor, "hsa-mir-4792" (miRBase Accession No. MI0017439, SEQ ID NO: 437).
[0256] As used herein, the term "hsa-miR-3656 gene" or "hsa-miR-3656" includes the hsa-miR-3656 gene (miRBase Accession No. MIMAT0018076) described in SEQ ID NO: 179, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res, 38, p6234-6246. Also, "hsa-miR-3656" is known to have a hairpin-like structure as its precursor, "hsa-mir-3656" (miRBase Accession No. MI0016056, SEQ ID NO: 438).
[0257] As used herein, the term "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" includes the hsa-miR-92a-2-5p gene (miRBase Accession No. MIMAT0004508) described in SEQ ID NO: 180, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Mourelatos Z et al., 2002, Genes Dev, 16, p720-728. Also, "hsa-miR-92a-2-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-92a-2" (miRBase Accession No. MI0000094, SEQ ID NO: 439).
[0258] As used herein, the term "hsa-miR-4466 gene" or "hsa-miR-4466" includes the hsa-miR-4466 gene described in SEQ ID NO: 181 (miRBase Accession No. MIMAT0018993), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4466" is known to have a hairpin-like structure as its precursor, "hsa-mir-4466" (miRBase Accession No. MI0016817, SEQ ID NO: 440).
[0259] As used herein, the term "hsa-miR-4513 gene" or "hsa-miR-4513" includes the hsa-miR-4513 gene described in SEQ ID NO: 182 (miRBase Accession No. MIMAT0019050), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4513" is known to have a hairpin-like structure as its precursor, "hsa-mir-4513" (miRBase Accession No. MI0016879, SEQ ID NO: 441).
[0260] As used herein, the term "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" includes the hsa-miR-6781-5p gene described in SEQ ID NO: 183 (miRBase Accession No. MIMAT0027462), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6781-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6781" (miRBase Accession No. MI0022626, SEQ ID NO: 442).
[0261] As used herein, the terms "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" include the hsa-miR-4649-5p gene (miRBase Accession No. MIMAT0019711) described in SEQ ID NO: 184, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4649-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4649" (miRBase Accession No. MI0017276, SEQ ID NO: 443).
[0262] As used herein, the terms "hsa-miR-6775-5p gene" or "hsa-miR-6775-5p" include the hsa-miR-6775-5p gene (miRBase Accession No. MIMAT0027450) described in SEQ ID NO: 185, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6775-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6775" (miRBase Accession No. MI0022620, SEQ ID NO: 444).
[0263] As used herein, the terms "hsa-miR-4651 gene" or "hsa-miR-4651" include the hsa-miR-4651 gene described in SEQ ID NO: 186 (miRBase Accession No. MIMAT0019715), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4651" is known to have a hairpin-like structure as its precursor, "hsa-mir-4651" (miRBase Accession No. MI0017279, SEQ ID NO: 445).
[0264] As used herein, the terms "hsa-miR-3195 gene" or "hsa-miR-3195" include the hsa-miR-3195 gene described in SEQ ID NO: 187 (miRBase Accession No. MIMAT0015079), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3195" is known to have a hairpin-like structure as its precursor, "hsa-mir-3195" (miRBase Accession No. MI0014240, SEQ ID NO: 446).
[0265] As used herein, the terms "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" include the hsa-miR-6726-5p gene described in SEQ ID NO: 188 (miRBase Accession No. MIMAT0027353), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6726-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6726" (miRBase Accession No. MI0022571, SEQ ID NO: 447).
[0266] As used herein, the terms "hsa-miR-6872-3p gene" or "hsa-miR-6872-3p" include the hsa-miR-6872-3p gene described in SEQ ID NO: 189 (miRBase Accession No. MIMAT0027645), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6872-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6872" (miRBase Accession No. MI0022719, SEQ ID NO: 448).
[0267] As used herein, the terms "hsa-miR-371a-5p gene" or "hsa-miR-371a-5p" include the hsa-miR-371a-5p gene described in SEQ ID NO: 190 (miRBase Accession No. MIMAT0004687), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Suh MR et al., 2004, Dev Biol, 270, p488-498. Also, "hsa-miR-371a-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-371a" (miRBase Accession No. MI0000779, SEQ ID NO: 449).
[0268] As used herein, the term "hsa-miR-6777-5p gene" or "hsa-miR-6777-5p" includes the hsa-miR-6777-5p gene described in SEQ ID NO: 191 (miRBase Accession No. MIMAT0027454), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6777-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6777" (miRBase Accession No. MI0022622, SEQ ID NO: 450).
[0269] As used herein, the term "hsa-miR-6789-5p gene" or "hsa-miR-6789-5p" includes the hsa-miR-6789-5p gene described in SEQ ID NO: 192 (miRBase Accession No. MIMAT0027478), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6789-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6789" (miRBase Accession No. MI0022634, SEQ ID NO: 451).
[0270] As used herein, the term "hsa-miR-7975 gene" or "hsa-miR-7975" includes the hsa-miR-7975 gene (miRBase Accession No. MIMAT0031178) described in SEQ ID NO: 193, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, 27, p1128-1141. Also, "hsa-miR-7975" is known to have a hairpin-like structure as its precursor, "hsa-mir-7975" (miRBase Accession No. MI0025751, SEQ ID NO: 452).
[0271] As used herein, the term "hsa-miR-6821-5p gene" or "hsa-miR-6821-5p" includes the hsa-miR-6821-5p gene (miRBase Accession No. MIMAT0027542) described in SEQ ID NO: 194, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6821-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6821" (miRBase Accession No. MI0022666, SEQ ID NO: 453).
[0272] As used herein, the term "hsa-miR-4534 gene" or "hsa-miR-4534" includes the hsa-miR-4534 gene described in SEQ ID NO: 195 (miRBase Accession No. MIMAT0019073), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4534" is known to have a hairpin-like structure as its precursor, "hsa-mir-4534" (miRBase Accession No. MI0016901, SEQ ID NO: 454).
[0273] As used herein, the term "hsa-miR-619-5p gene" or "hsa-miR-619-5p" includes the hsa-miR-619-5p gene described in SEQ ID NO: 196 (miRBase Accession No. MIMAT0026622), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-619-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-619" (miRBase Accession No. MI0003633, SEQ ID NO: 455).
[0274] As used herein, the term "hsa-miR-7107-5p gene" or "hsa-miR-7107-5p" includes the hsa-miR-7107-5p gene (miRBase Accession No. MIMAT0028111) described in SEQ ID NO: 197, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-7107-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7107" (miRBase Accession No. MI0022958, SEQ ID NO: 456).
[0275] As used herein, the term "hsa-miR-1228-3p gene" or "hsa-miR-1228-3p" includes the hsa-miR-1228-3p gene (miRBase Accession No. MIMAT0005583) described in SEQ ID NO: 198, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336. Also, "hsa-miR-1228-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 457).
[0276] As used herein, the terms "hsa-miR-6774-5p gene" or "hsa-miR-6774-5p" include the hsa-miR-6774-5p gene (miRBase Accession No. MIMAT0027448) described in SEQ ID NO: 199, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6774-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6774" (miRBase Accession No. MI0022619, SEQ ID NO: 458).
[0277] As used herein, the terms "hsa-miR-6805-5p gene" or "hsa-miR-6805-5p" include the hsa-miR-6805-5p gene (miRBase Accession No. MIMAT0027510) described in SEQ ID NO: 200, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6805-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6805" (miRBase Accession No. MI0022650, SEQ ID NO: 459).
[0278] As used herein, the term "hsa-miR-23a-3p gene" or "hsa-miR-23a-3p" includes the hsa-miR-23a-3p gene (miRBase Accession No. MIMAT0000078) described in SEQ ID NO: 201, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science, Vol. 294, p853-858. Also, "hsa-miR-23a-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-23a" (miRBase Accession No. MI0000079, SEQ ID NO: 460).
[0279] As used herein, the term "hsa-miR-4665-5p gene" or "hsa-miR-4665-5p" includes the hsa-miR-4665-5p gene (miRBase Accession No. MIMAT0019739) described in SEQ ID NO: 202, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, p78-86. Also, "hsa-miR-4665-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4665" (miRBase Accession No. MI0017295, SEQ ID NO: 461).
[0280] As used herein, the term "hsa-miR-4505 gene" or "hsa-miR-4505" encompasses the hsa-miR-4505 gene described in SEQ ID NO: 203 (miRBase Accession No. MIMAT0019041), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, pp. e118-e127. Also, "hsa-miR-4505" is known to have a hairpin-like structure as its precursor, "hsa-mir-4505" (miRBase Accession No. MI0016868, SEQ ID NO: 462).
[0281] As used herein, the term "hsa-miR-4638-5p gene" or "hsa-miR-4638-5p" encompasses the hsa-miR-4638-5p gene described in SEQ ID NO: 204 (miRBase Accession No. MIMAT0019695), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Also, "hsa-miR-4638-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4638" (miRBase Accession No. MI0017265, SEQ ID NO: 463).
[0282] As used herein, the terms "hsa-miR-24-3p gene" or "hsa-miR-24-3p" include the hsa-miR-24-3p gene described in SEQ ID NO: 205 (miRBase Accession No. MIMAT0000080), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science, Vol. 294, p853-858. Also, "hsa-miR-24-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-24-1, hsa-mir-24-2" (miRBase Accession No. MI0000080, MI0000081, SEQ ID NO: 464, 465).
[0283] As used herein, the terms "hsa-miR-3135b gene" or "hsa-miR-3135b" include the hsa-miR-3135b gene described in SEQ ID NO: 206 (miRBase Accession No. MIMAT0018985), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-miR-3135b" is known to have a hairpin-like structure as its precursor, "hsa-mir-3135b" (miRBase Accession No. MI0016809, SEQ ID NO: 466).
[0284] As used herein, the terms "hsa-miR-4745-5p gene" or "hsa-miR-4745-5p" include the hsa-miR-4745-5p gene described in SEQ ID NO: 207 (miRBase Accession No. MIMAT0019878), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4745-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4745" (miRBase Accession No. MI0017384, SEQ ID NO: 467).
[0285] As used herein, the terms "hsa-miR-128-1-5p gene" or "hsa-miR-128-1-5p" include the hsa-miR-128-1-5p gene described in SEQ ID NO: 208 (miRBase Accession No. MIMAT0026477), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, 12, p735-739. Also, "hsa-miR-128-1-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-128-1" (miRBase Accession No. MI0000447, SEQ ID NO: 468).
[0286] As used herein, the term "hsa-miR-4476 gene" or "hsa-miR-4476" includes the hsa-miR-4476 gene (miRBase Accession No. MIMAT0019003) described in SEQ ID NO: 209, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4476" is known to have a hairpin-like structure as its precursor, "hsa-mir-4476" (miRBase Accession No. MI0016828, SEQ ID NO: 469).
[0287] As used herein, the term "hsa-miR-4687-3p gene" or "hsa-miR-4687-3p" includes the hsa-miR-4687-3p gene (miRBase Accession No. MIMAT0019775) described in SEQ ID NO: 210, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4687-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4687" (miRBase Accession No. MI0017319, SEQ ID NO: 470).
[0288] As used herein, the term "hsa-miR-3665 gene" or "hsa-miR-3665" includes the hsa-miR-3665 gene (miRBase Accession No. MIMAT0018087) described in SEQ ID NO: 211, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Xie X et al., 2005, Nature, 434, p338-345. Also, "hsa-miR-3665" is known to have a hairpin-like structure as its precursor, "hsa-mir-3665" (miRBase Accession No. MI0016066, SEQ ID NO: 471).
[0289] As used herein, the terms "hsa-miR-6806-5p gene" or "hsa-miR-6806-5p" include the hsa-miR-6806-5p gene described in SEQ ID NO: 212 (miRBase Accession No. MIMAT0027512), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6806-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6806" (miRBase Accession No. MI0022651, SEQ ID NO: 472).
[0290] As used herein, the terms "hsa-miR-3937 gene" or "hsa-miR-3937" include the hsa-miR-3937 gene described in SEQ ID NO: 213 (miRBase Accession No. MIMAT0018352), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Liao JY et al., 2010, PLoS One, 5, e10563. Also, "hsa-miR-3937" is known to have a hairpin-like structure as its precursor, "hsa-mir-3937" (miRBase Accession No. MI0016593, SEQ ID NO: 473).
[0291] As used herein, the terms "hsa-miR-711 gene" or "hsa-miR-711" include the hsa-miR-711 gene (miRBase Accession No. MIMAT0012734) described in SEQ ID NO: 214, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Artzi S et al., 2008, BMC Bioinformatics, 9, p39. Also, "hsa-miR-711" is known to have a hairpin-like structure as its precursor, "hsa-mir-711" (miRBase Accession No. MI0012488, SEQ ID NO: 474).
[0292] As used herein, the terms "hsa-miR-3141 gene" or "hsa-miR-3141" include the hsa-miR-3141 gene (miRBase Accession No. MIMAT0015010) described in SEQ ID NO: 215, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3141" is known to have a hairpin-like structure as its precursor, "hsa-mir-3141" (miRBase Accession No. MI0014165, SEQ ID NO: 475).
[0293] As used herein, the terms "hsa-miR-3188 gene" or "hsa-miR-3188" include the hsa-miR-3188 gene (miRBase Accession No. MIMAT0015070) described in SEQ ID NO: 216, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3188" is known to have a hairpin-like structure as its precursor, "hsa-mir-3188" (miRBase Accession No. MI0014232, SEQ ID NO: 476).
[0294] As used herein, the terms "hsa-miR-4281 gene" or "hsa-miR-4281" include the hsa-miR-4281 gene described in SEQ ID NO: 217 (miRBase Accession No. MIMAT0016907), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4281" is known to have a hairpin-like structure as its precursor, "hsa-mir-4281" (miRBase Accession No. MI0015885, SEQ ID NO: 477).
[0295] As used herein, the terms "hsa-miR-5196-5p gene" or "hsa-miR-5196-5p" include the hsa-miR-5196-5p gene described in SEQ ID NO: 218 (miRBase Accession No. MIMAT0021128), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Schotte D et al., 2011, Leukemia, 25, p1389-1399. Also, "hsa-miR-5196-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-5196" (miRBase Accession No. MI0018175, SEQ ID NO: 478).
[0296] As used herein, the terms "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" include the hsa-miR-6880-5p gene (miRBase Accession No. MIMAT0027660) described in SEQ ID NO: 219, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6880-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6880" (miRBase Accession No. MI0022727, SEQ ID NO: 479).
[0297] As used herein, the terms "hsa-miR-3960 gene" or "hsa-miR-3960" include the hsa-miR-3960 gene (miRBase Accession No. MIMAT0019337) described in SEQ ID NO: 220, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Hu R et al., 2011, J Biol Chem, 286, p12328-12339. Also, "hsa-miR-3960" is known to have a hairpin-like structure as its precursor, "hsa-mir-3960" (miRBase Accession No. MI0016964, SEQ ID NO: 480).
[0298] As used herein, the term "hsa-miR-3648 gene" or "hsa-miR-3648" includes the hsa-miR-3648 gene (miRBase Accession No. MIMAT0018068) described in SEQ ID NO: 221, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, p6234-6246. Also, "hsa-miR-3648" is known to have "hsa-mir-3648-1, hsa-mir-3648-2" (miRBase Accession No. MI0016048, MI0031512, SEQ ID NO: 481, 482) with a hairpin-like structure as its precursor.
[0299] As used herein, the term "hsa-miR-6721-5p gene" or "hsa-miR-6721-5p" includes the hsa-miR-6721-5p gene (miRBase Accession No. MIMAT0025852) described in SEQ ID NO: 222, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, p330-335. Also, "hsa-miR-6721-5p" is known to have "hsa-mir-6721" (miRBase Accession No. MI0022556, SEQ ID NO: 483) with a hairpin-like structure as its precursor.
[0300] As used herein, the terms "hsa-miR-4492 gene" or "hsa-miR-4492" include the hsa-miR-4492 gene (miRBase Accession No. MIMAT0019027) described in SEQ ID NO: 223, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, pp. e118-e127. Also, "hsa-miR-4492" is known to have a hairpin-like structure as its precursor, "hsa-mir-4492" (miRBase Accession No. MI0016854, SEQ ID NO: 484).
[0301] As used herein, the terms "hsa-miR-744-5p gene" or "hsa-miR-744-5p" include the hsa-miR-744-5p gene (miRBase Accession No. MIMAT0004945) described in SEQ ID NO: 224, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Also, "hsa-miR-744-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-744" (miRBase Accession No. MI0005559, SEQ ID NO: 485).
[0302] As used herein, the term "hsa-miR-7704 gene" or "hsa-miR-7704" includes the hsa-miR-7704 gene (miRBase Accession No. MIMAT0030019) described in SEQ ID NO: 225, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Swaminathan S et al., 2013, Biochem Biophys Res Commun, 434: 228-234. Also, "hsa-miR-7704" is known to have a hairpin-like structure as its precursor, "hsa-mir-7704" (miRBase Accession No. MI0025240, SEQ ID NO: 486).
[0303] As used herein, the term "hsa-miR-4749-5p gene" or "hsa-miR-4749-5p" includes the hsa-miR-4749-5p gene (miRBase Accession No. MIMAT0019885) described in SEQ ID NO: 226, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71: 78-86. Also, "hsa-miR-4749-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4749" (miRBase Accession No. MI0017388, SEQ ID NO: 487).
[0304] As used herein, the term "hsa-miR-6794-5p gene" or "hsa-miR-6794-5p" includes the hsa-miR-6794-5p gene (miRBase Accession No. MIMAT0027488) described in SEQ ID NO: 227, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6794-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6794" (miRBase Accession No. MI0022639, SEQ ID NO: 488).
[0305] As used herein, the term "hsa-miR-6511a-5p gene" or "hsa-miR-6511a-5p" includes the hsa-miR-6511a-5p gene (miRBase Accession No. MIMAT0025478) described in SEQ ID NO: 228, as well as homologs or orthologs of other species. The gene can be obtained by the method described by Joyce CE et al., 2011, Hum Mol Genet, 20, p4025-4040. Also, "hsa-miR-6511a-5p" is known to have 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: 489, 490, 491, 492).
[0306] As used herein, the term "hsa-miR-6824-5p gene" or "hsa-miR-6824-5p" includes the hsa-miR-6824-5p gene (miRBase Accession No. MIMAT0027548) described in SEQ ID NO: 229, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6824-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6824" (miRBase Accession No. MI0022669, SEQ ID NO: 493).
[0307] As used herein, the term "hsa-miR-762 gene" or "hsa-miR-762" includes the hsa-miR-762 gene (miRBase Accession No. MIMAT0010313) described in SEQ ID NO: 230, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, 16, p1289-1298. Also, "hsa-miR-762" is known to have a hairpin-like structure as its precursor, "hsa-mir-762" (miRBase Accession No. MI0003892, SEQ ID NO: 494).
[0308] As used herein, the term "hsa-miR-6836-3p gene" or "hsa-miR-6836-3p" includes the hsa-miR-6836-3p gene (miRBase Accession No. MIMAT0027575) described in SEQ ID NO: 231, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6836-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6836" (miRBase Accession No. MI0022682, SEQ ID NO: 495).
[0309] As used herein, the term "hsa-miR-6727-5p gene" or "hsa-miR-6727-5p" includes the hsa-miR-6727-5p gene (miRBase Accession No. MIMAT0027355) described in SEQ ID NO: 232, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6727-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6727" (miRBase Accession No. MI0022572, SEQ ID NO: 496).
[0310] As used herein, the terms "hsa-miR-4739 gene" or "hsa-miR-4739" include the hsa-miR-4739 gene (miRBase Accession No. MIMAT0019868) described in SEQ ID NO: 233, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78 - 86. Also, "hsa-miR-4739" is known to have a hairpin-like structure as its precursor, "hsa-mir-4739" (miRBase Accession No. MI0017377, SEQ ID NO: 497).
[0311] As used herein, the terms "hsa-miR-7977 gene" or "hsa-miR-7977" include the hsa-miR-7977 gene (miRBase Accession No. MIMAT0031180) described in SEQ ID NO: 234, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, 27, p1128 - 1141. Also, "hsa-miR-7977" is known to have a hairpin-like structure as its precursor, "hsa-mir-7977" (miRBase Accession No. MI0025753, SEQ ID NO: 498).
[0312] As used herein, the terms "hsa-miR-4484 gene" or "hsa-miR-4484" include the hsa-miR-4484 gene (miRBase Accession No. MIMAT0019018) described in SEQ ID NO: 235, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118 - e127. Also, "hsa-miR-4484" is known to have a hairpin-like structure as its precursor, "hsa-mir-4484" (miRBase Accession No. MI0016845, SEQ ID NO: 499).
[0313] As used herein, the terms "hsa-miR-6515-3p gene" or "hsa-miR-6515-3p" include the hsa-miR-6515-3p gene described in SEQ ID NO: 236 (miRBase Accession No. MIMAT0025487), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Joyce CE et al., 2011, Hum Mol Genet, 20, p4025-4040. Also, "hsa-miR-6515-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6515" (miRBase Accession No. MI0022227, SEQ ID NO: 500).
[0314] As used herein, the terms "hsa-miR-373-5p gene" or "hsa-miR-373-5p" include the hsa-miR-373-5p gene described in SEQ ID NO: 237 (miRBase Accession No. MIMAT0000725), as well as homologs or orthologs of other species. The gene can be obtained by the method described by Suh MR et al., 2004, Dev Biol, 270, p488-498. Also, "hsa-miR-373-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-373" (miRBase Accession No. MI0000781, SEQ ID NO: 501).
[0315] As used herein, the terms "hsa-miR-4258 gene" or "hsa-miR-4258" include the hsa-miR-4258 gene described in SEQ ID NO: 238 (miRBase Accession No. MIMAT0016879), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4258" is known to have a hairpin-like structure as its precursor, "hsa-mir-4258" (miRBase Accession No. MI0015857, SEQ ID NO: 502).
[0316] As used herein, the terms "hsa-miR-4674 gene" or "hsa-miR-4674" include the hsa-miR-4674 gene described in SEQ ID NO: 239 (miRBase Accession No. MIMAT0019756), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4674" is known to have a hairpin-like structure as its precursor, "hsa-mir-4674" (miRBase Accession No. MI0017305, SEQ ID NO: 503).
[0317] As used herein, the term "hsa-miR-3180 gene" or "hsa-miR-3180" includes the hsa-miR-3180 gene described in SEQ ID NO: 240 (miRBase Accession No. MIMAT0018178), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Also, "hsa-miR-3180" is known to have "hsa-mir-3180-4, hsa-mir-3180-5" (miRBase Accession No. MI0016408, MI0016409, SEQ ID NOs: 504, 505) with a hairpin-like structure as its precursor.
[0318] As used herein, the term "hsa-miR-6076 gene" or "hsa-miR-6076" includes the hsa-miR-6076 gene described in SEQ ID NO: 241 (miRBase Accession No. MIMAT0023701), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Voellenkle C et al., 2012, RNA, Vol. 18, p472-484. Also, "hsa-miR-6076" is known to have "hsa-mir-6076" (miRBase Accession No. MI0020353, SEQ ID NO: 506) with a hairpin-like structure as its precursor.
[0319] As used herein, the terms "hsa-miR-1238-5p gene" or "hsa-miR-1238-5p" include the hsa-miR-1238-5p gene (miRBase Accession No. MIMAT0022947) described in SEQ ID NO: 242, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28: p328-336. Also, "hsa-miR-1238-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1238" (miRBase Accession No. MI0006328, SEQ ID NO: 507).
[0320] As used herein, the terms "hsa-miR-4463 gene" or "hsa-miR-4463" include the hsa-miR-4463 gene (miRBase Accession No. MIMAT0018987) described in SEQ ID NO: 243, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116: e118-e127. Also, "hsa-miR-4463" is known to have a hairpin-like structure as its precursor, "hsa-mir-4463" (miRBase Accession No. MI0016811, SEQ ID NO: 508).
[0321] As used herein, the terms "hsa-miR-4486 gene" or "hsa-miR-4486" include the hsa-miR-4486 gene (miRBase Accession No. MIMAT0019020) described in SEQ ID NO: 244, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116: e118-e127. Also, "hsa-miR-4486" is known to have a hairpin-like structure as its precursor, "hsa-mir-4486" (miRBase Accession No. MI0016847, SEQ ID NO: 509).
[0322] As used herein, the terms "hsa-miR-4730 gene" or "hsa-miR-4730" include the hsa-miR-4730 gene (miRBase Accession No. MIMAT0019852) described in SEQ ID NO: 245, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78 - 86. Also, "hsa-miR-4730" is known to have a hairpin-like structure as its precursor, "hsa-mir-4730" (miRBase Accession No. MI0017367, SEQ ID NO: 510).
[0323] As used herein, the terms "hsa-miR-6766-3p gene" or "hsa-miR-6766-3p" include the hsa-miR-6766-3p gene (miRBase Accession No. MIMAT0027433) described in SEQ ID NO: 246, as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634 - 1645. Also, "hsa-miR-6766-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6766" (miRBase Accession No. MI0022611, SEQ ID NO: 511).
[0324] As used herein, the terms "hsa-miR-4286 gene" or "hsa-miR-4286" include the hsa-miR-4286 gene described in SEQ ID NO: 247 (miRBase Accession No. MIMAT0016916), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4286" is known to have a hairpin-like structure as its precursor, "hsa-mir-4286" (miRBase Accession No. MI0015894, SEQ ID NO: 512).
[0325] As used herein, the terms "hsa-miR-6511a-5p gene" or "hsa-miR-6511a-5p" include the hsa-miR-6511a-5p gene described in SEQ ID NO: 248 (miRBase Accession No. MIMAT0025478), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet, 20, p4025-4040. Also, "hsa-miR-6511a-5p" is known to have 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: 513, 514, 515, 516).
[0326] As used herein, the term "hsa-miR-4739 gene" or "hsa-miR-4739" includes the hsa-miR-4739 gene described in SEQ ID NO: 249 (miRBase Accession No. MIMAT0019868), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4739" is known to have a hairpin-like structure as its precursor, "hsa-mir-4739" (miRBase Accession No. MI0017377, SEQ ID NO: 517).
[0327] As used herein, the term "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" includes the hsa-miR-6749-5p gene described in SEQ ID NO: 250 (miRBase Accession No. MIMAT0027398), as well as homologs or orthologs of other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6749-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6749" (miRBase Accession No. MI0022594, SEQ ID NO: 518).
[0328] Furthermore, when mature miRNAs are excised from RNA precursors with a hairpin-like structure to become mature miRNAs, one to several bases at the front and back of the sequence may be excised shorter or longer, or base substitutions may occur to form variants, which are called isomiRs (Morin RD. et al., 2008, Genome Res., Vol. 18, p. 610-621). In miRBase Release 20, in addition to the base sequences represented by any of SEQ ID NOs: 1 to 250, variants and fragments of base sequences represented by any of SEQ ID NOs: 519 to 812, which are called various isomiRs, are also shown. These variants can also be obtained as miRNAs with the base sequences represented by any of SEQ ID NOs: 1 to 250. That is, among the variants of the polynucleotides consisting of the base sequences represented by SEQ ID NOs: 2, 3, 6, 7, 8, 11, 12, 13, 15, 19, 20, 25, 26, 27, 29, 31, 32, 37, 44, 45, 46, 47, 48, 49, 51, 52, 53, 54, 55, 56, 57, 59, 60, 61, 62, 63, 71, 72, 73, 74, 76, 77, 78, 79, 83, 84, 86, 87, 88, 89, 90, 92, 94, 98, 102, 105, 106, 108, 111, 112, 113, 114, 116, 117, 118, 122, 123, 124, 128, 129, 133, 134, 135, 136, 137, 140, 141, 145, 146, 147, 148, 149, 150, 151, 153, 154, 155, 157, 158, 159, 160, 161, 162, 163, 166, 167, 168, 169, 176, 177, 178, 179, 180, 181, 182, 184, 186, 187, 190, 193, 196, 198, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 214, 215, 216, 217, 218, 220, 221, 222, 223, 224, 226, 228, 233, 235, 236, 237, 239, 240, 243, 244, 245, 247, 248, and 249, or the base sequences in which u is t in the base sequences, for example, as the longest variants registered in miRBase Release 20, SEQ ID NOs: 519, 521, 523, 525, 527, 529, 531, 533, 535, 537,Polynucleotides represented by 539, 541, 543, 545, 547, 549, 551, 553, 555, 557, 559, 561, 563, 565, 567, 569, 571, 573, 575, 577, 579, 581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625, 627, 629, 631, 633, 635, 637, 639, 641, 643, 645, 647, 649, 651, 653, 655, 657, 659, 661, 663, 665, 667, 669, 671, 673, 675, 677, 679, 681, 683, 685, 687, 689, 691, 693, 695, 697, 699, 701, 703, 705, 707, 709, 711, 713, 715, 717, 719, 721, 723, 725, 727, 729, 731, 733, 735, 737, 739, 741, 743, 745, 747, 749, 751, 753, 755, 757, 759, 761, 763, 765, 767, 769, 771, 773, 775, 777, 779, 781, 783, 785, 787, 789, 791, 793, 795, 797, 799, 801, 803, 805, 807, 809, and 811 are included. Also, SEQ ID NOs: 2, 3, 6, 7, 8, 11, 12, 13, 15, 19, 20, 25, 26, 27, 29, 31, 32, 37, 44, 45, 46, 47, 48, 49, 51, 52, 53, 54, 55, 56, 57, 59, 60, 61, 62, 63, 71, 72, 73, 74, 76, 77, 78, 79, 83, 84, 86, 87, 88, 89, 90, 92, 94, 98, 102, 105, 106, 108, 111, 112, 113, 114, 116, 117, 118, 122, 123, 124, 128, 129, 133, 134, 135, 136, 137, 140, 141, 145, 146, 147, 148, 149, 150, 151, 153, 154, 155, 157, 158, 159, 160, 161, 162, 163, 166, 167, 168, 169, 176, 177, 178, 179, 180, 181, 182, 184, 186, 187, 190, 193, 196, 198, 201, 202, 203, 204, 205, 206, 207, 208,Among the variants of the polynucleotide consisting of the base sequences represented by 209, 210, 211, 214, 215, 216, 217, 218, 220, 221, 222, 223, 224, 226, 228, 233, 235, 236, 237, 239, 240, 243, 244, 245, 247, 248, and 249, or the base sequences in which u is t in the said base sequences, for example, as the shortest variants registered in miRBase Release 20, the polynucleotides of the sequences represented by SEQ ID NO: 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, 566, 568, 570, 572, 574, 576, 578, 580, 582, 584, 586, 588, 590, 592, 594, 596, 598, 600, 602, 604, 606, 608, 610, 612, 614, 616, 618, 620, 622, 624, 626, 628, 630, 632, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 686, 688, 690, 692, 694, 696, 698, 700, 702, 704, 706, 708, 710, 712, 714, 716, 718, 720, 722, 724, 726, 728, 730, 732, 734, 736, 738, 740, 742, 744, 746, 748, 750, 752, 754, 756, 758, 760, 762, 764, 766, 768, 770, 772, 774, 776, 778, 780, 782, 784, 786, 788, 790, 792, 794, 796, 798, 800, 802, 804, 806, 808, 810, and 812 are included. Also, in addition to these variants and fragments, those registered in miRBase, SEQ ID NO: 2, 3, 6, 7, 8, 11, 12, 13, 15, 19, 20, 25, 26, 27, 29, 31, 32, 37, 44, 45, 46, 47, 48, 49, 51, 52, 53, 54, 55, 56, 57, 59, 60, 61, 62, 63, 71, 72, 73, 74, 76, 77, 78, 79, 83, 84, 86, 87, 88,Polynucleotides that are various isomiRs of 89, 90, 92, 94, 98, 102, 105, 106, 108, 111, 112, 113, 114, 116, 117, 118, 122, 123, 124, 128, 129, 133, 134, 135, 136, 137, 140, 141, 145, 146, 147, 148, 149, 150, 151, 153, 154, 155, 157, 158, 159, 160, 161, 162, 163, 166, 167, 168, 169, 176, 177, 178, 179, 180, 181, 182, 184, 186, 187, 190, 193, 196, 198, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 214, 215, 216, 217, 218, 220, 221, 222, 223, 224, 226, 228, 233, 235, 236, 237, 239, 240, 243, 244, 245, 247, 248, and 249 are included. Further, examples of polynucleotides containing the base sequences represented by any of SEQ ID NOs: 1 to 250 include polynucleotides represented by any of SEQ ID NOs: 251 to 518, which are their respective precursors.,
[0329] The names of the genes represented by SEQ ID NOs: 1 to 812 and the miRBase Accession No. (registration number) are shown in Table 1.
[0330] As used herein, "specifically bindable" means that the nucleic acid probe or primer used in the present invention binds to a specific target nucleic acid and cannot substantially bind to other nucleic acids.
[0331]
Table 1
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[0349] This specification incorporates the disclosure of Japanese Patent Application No. 2016-073132 (filing date: March 31, 2016), which is the basis for the priority of this application.
Advantages of the Invention
[0350] According to the present invention, it has become possible to easily and accurately detect early-stage pancreatic cancer or pancreatic cancer precursor lesions.
[0351] For example, by using the measured values of the expression levels of several miRNAs in the blood, serum, and / or plasma of patients that can be collected in a minimally invasive manner as an index, it is possible to easily detect whether a patient has early-stage pancreatic cancer or a pancreatic cancer precursor lesion.
Brief Description of the Drawings
[0352]
Figure 1
Figure 2
Figure 3
Figure 4
Embodiments for Carrying Out the Invention
[0353] The present invention will be further specifically described below 1. Target Nucleic Acid for Early Pancreatic Cancer or Pancreatic Cancer Precursor Lesion Using the nucleic acid probes or primers for detecting early pancreatic cancer or pancreatic cancer precursor lesions as defined above of the present invention, the main target nucleic acids as early pancreatic cancer or pancreatic cancer precursor lesion markers for detecting the presence and / or absence of early pancreatic cancer or pancreatic cancer precursor lesions or early pancreatic cancer or pancreatic cancer precursor lesion cells include hsa-miR-6784-5p, hsa-miR-1181, hsa-miR-671-5p, hsa-miR-6857-5p, hsa-miR-4276, hsa-miR-1914-3p, hsa-miR-149-3p, hsa-miR-937-5p, hsa-miR-4675, hsa-miR-6795-5p, hsa-miR-4731-5p, hsa-miR-5090, hsa-miR-3620-5p, hsa-miR-1343-5p, hsa-miR-6717-5p, hsa-miR-6825-5p, hsa-miR-6738-5p, hsa-miR-6769a-5p, hsa-miR-4728-5p, hsa-miR-652-5p, hsa-miR-4257, hsa-miR-6785-5p, hsa-miR-7110-5p, hsa-miR-6887-5p, hsa-miR-887-3p, hsa-miR-1228-5p, hsa-miR-5572, hsa-miR-6782-5p, hsa-miR-4298, hsa-miR-6786-5p, hsa-miR-5010-5p, hsa-miR-6087, hsa-miR-6765-5p, hsa-miR-6732-5p, hsa-miR-6787-5p, hsa-miR-6737-5p, hsa-miR-128-2-5p, hsa-miR-4270, hsa-miR-6861-5p, hsa-miR-6756-5p, hsa-miR-1229-5p, hsa-miR-6891-5p, hsa-miR-6848-5p, hsa-miR-1237-5p, hsa-miR-30c-1-3p, hsa-miR-1233-5p, hsa-miR-211-3p, hsa-miR-4758-5p, hsa-miR-614, hsa-miR-6746-5p, hsa-miR-1915-5p, hsa-miR-4688, hsa-miR-3917, hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126, hsa-miR-135a-3p,Comprising at least one miRNA selected from the group consisting of hsa-miR-8063, hsa-miR-5698, hsa-miR-6089, hsa-miR-498, hsa-miR-296-3p, hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p, hsa-miR-6803-5p, hsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p, hsa-miR-6798-5p, hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p, hsa-miR-4690-5p, hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448, hsa-miR-2110, hsa-miR-4706, hsa-miR-7845-5p, hsa-miR-6808-5p, hsa-miR-4447, hsa-miR-6869-5p, hsa-miR-6794-5p, hsa-miR-6511a-5p, hsa-miR-6824-5p, hsa-miR-6766-3p, hsa-miR-6511a-5p, and hsa-miR-6749-5p.,
[0354] Other early pancreatic cancer or pancreatic cancer precursor lesion markers that can be combined with these miRNAs, namely, hsa-miR-1908-5p, hsa-miR-6729-5p, hsa-miR-5195-3p, hsa-miR-638, hsa-miR-6125, hsa-miR-3178, hsa-miR-3196, hsa-miR-8069, hsa-miR-4723-5p, hsa-miR-4746-3p, hsa-miR-4689, hsa-miR-6816-5p, hsa-miR-6757-5p, hsa-miR-7109-5p, hsa-miR-6724-5p, hsa-miR-1225-3p, hsa-miR-6875-5p, hsa-miR-7108-5p, hsa-miR-4508, hsa-miR-6085, hsa-miR-6779-5p, hsa-miR-642a-3p, hsa-miR-4695-5p, hsa-miR-7847-3p, hsa-miR-3197, hsa-miR-6769b-5p, hsa-miR-7641, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-2861, hsa-miR-3940-5p, hsa-miR-1203, hsa-miR-615-5p, hsa-miR-4787-5p, hsa-miR-1343-3p, hsa-miR-6813-5p, hsa-miR-1225-5p, hsa-miR-602, hsa-miR-4488, hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294, hsa-miR-1231, hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718, hsa-miR-6780b-5p, hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741, hsa-miR-4467, hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673, hsa-miR-3184-5p, hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a, hsa-miR-6791-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p, hsa-miR-4417, hsa-miR-4449hsa-miR-4707-3p, hsa-miR-3180-3p, hsa-miR-5585-3p, hsa-miR-1268a, hsa-miR-8072, hsa-miR-296-5p, hsa-miR-204-3p, hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290, hsa-miR-3622a-5p, hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131, hsa-miR-4648, hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p, hsa-miR-3162-5p, hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p, hsa-miR-8089, hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p, hsa-miR-6799-5p, hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p, hsa-miR-4792, hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466, hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5p, hsa-miR-4651, hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p, hsa-miR-371a-5p, hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975, hsa-miR-6821-5p, hsa-miR-4534, hsa-miR-619-5p, hsa-miR-7107-5p, hsa-miR-1228-3p, hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p, hsa-miR-4665-5p, hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p, hsa-miR-3135b, hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476, hsa-miR-4687-3p, hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937, hsa-miR-711At least one miRNA selected from the group consisting of hsa-miR-3141, hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5p, hsa-miR-6880-5p, hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p, hsa-miR-4492, hsa-miR-744-5p, hsa-miR-7704, hsa-miR-4749-5p, hsa-miR-762, hsa-miR-6836-3p, hsa-miR-6727-5p, hsa-miR-4739, hsa-miR-7977, hsa-miR-4484, hsa-miR-6515-3p, hsa-miR-373-5p, hsa-miR-4258, hsa-miR-4674, hsa-miR-3180, hsa-miR-6076, hsa-miR-1238-5p, hsa-miR-4463, hsa-miR-4486, hsa-miR-4730, hsa-miR-4286, and hsa-miR-4739 can also preferably be used as the target nucleic acid.,
[0355] The above-mentioned miRNAs include, for example, human genes containing nucleotide sequences represented by any of SEQ ID NOs: 1 to 250 (i.e., hsa-miR-6784-5p, hsa-miR-1181, hsa-miR-671-5p, hsa-miR-6857-5p, hsa-miR-4276, hsa-miR-1914-3p, hsa-miR-149-3p, hsa-miR-937-5p, hsa-miR-4675, hsa-miR-6795-5p, hsa-miR-4731-5p, hsa-miR-5090, hsa-miR-3620-5p, hsa-miR-1343-5p, hsa-miR-6717-5p, hsa-miR-6825-5p, hsa-miR-6738-5p, hsa-miR-6769a-5p, hsa-miR-4728-5p, hsa-miR-652-5p, hsa-miR-4257, hsa-miR-6785-5p, hsa-miR-7110-5p, hsa-miR-6887-5p, hsa-miR-887-3p, hsa-miR-1228-5p, hsa-miR-5572, hsa-miR-6782-5p, hsa-miR-4298, hsa-miR-6786-5p, hsa-miR-5010-5p, hsa-miR-6087, hsa-miR-6765-5p, hsa-miR-6732-5p, hsa-miR-6787-5p, hsa-miR-6737-5p, hsa-miR-128-2-5p, hsa-miR-4270, hsa-miR-6861-5p, hsa-miR-6756-5p, hsa-miR-1229-5p, hsa-miR-6891-5p, hsa-miR-6848-5p, hsa-miR-1237-5p, hsa-miR-30c-1-3p, hsa-miR-1233-5p, hsa-miR-211-3p, hsa-miR-4758-5p, hsa-miR-614, hsa-miR-6746-5p, hsa-miR-1915-5p, hsa-miR-4688, hsa-miR-3917, hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126, hsa-miR-135a-3p, hsa-miR-8063, hsa-miR-5698, hsa-miR-6089, hsa-miR-498, hsa-miR-296-3p, respectively).hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p, hsa-miR-6803-5p, hsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p, hsa-miR-6798-5p, hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p, hsa-miR-4690-5p, hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448, hsa-miR-2110, hsa-miR-4706, hsa-miR-7845-5p, hsa-miR-6808-5p, hsa-miR-4447, hsa-miR-6869-5p, hsa-miR-1908-5p, hsa-miR-6729-5p, hsa-miR-5195-3p, hsa-miR-638, hsa-miR-6125, hsa-miR-3178, hsa-miR-3196, hsa-miR-8069, hsa-miR-4723-5p, hsa-miR-4746-3p, hsa-miR-4689, hsa-miR-6816-5p, hsa-miR-6757-5p, hsa-miR-7109-5p, hsa-miR-6724-5p, hsa-miR-1225-3p, hsa-miR-6875-5p, hsa-miR-7108-5p, hsa-miR-4508, hsa-miR-6085, hsa-miR-6779-5p, hsa-miR-642a-3p, hsa-miR-4695-5p, hsa-miR-7847-3p, hsa-miR-3197, hsa-miR-6769b-5p, hsa-miR-7641, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-2861, hsa-miR-3940-5p, hsa-miR-1203, hsa-miR-615-5p, hsa-miR-4787-5p, hsa-miR-1343-3p, hsa-miR-6813-5p, hsa-miR-1225-5p, hsa-miR-602, hsa-miR-4488, hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294, hsa-miR-1231, hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718hsa-miR-6780b-5p, hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741, hsa-miR-4467, hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673, hsa-miR-3184-5p, hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a, hsa-miR-6791-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p, hsa-miR-4417, hsa-miR-4449, hsa-miR-4707-3p, hsa-miR-3180-3p, hsa-miR-5585-3p, hsa-miR-1268a, hsa-miR-8072, hsa-miR-296-5p, hsa-miR-204-3p, hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290, hsa-miR-3622a-5p, hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131, hsa-miR-4648, hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p, hsa-miR-3162-5p, hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p, hsa-miR-8089, hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p, hsa-miR-6799-5p, hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p, hsa-miR-4792, hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466, hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5p, hsa-miR-4651, hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p, hsa-miR-371a-5p, hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975, hsa-miR-6821-5p, hsa-miR-4534, hsa-miR-619-5phsa-miR-7107-5p, hsa-miR-1228-3p, hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p, hsa-miR-4665-5p, hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p, hsa-miR-3135b, hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476, hsa-miR-4687-3p, hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937, hsa-miR-711, hsa-miR-3141, hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5p, hsa-miR-6880-5p, hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p, hsa-miR-4492, hsa-miR-744-5p, hsa-miR-7704, hsa-miR-4749-5p, hsa-miR-6794-5p, hsa-miR-6511a-5p, hsa-miR-6824-5p, hsa-miR-762, hsa-miR-6836-3p, hsa-miR-6727-5p, hsa-miR-4739, hsa-miR-7977, hsa-miR-4484, hsa-miR-6515-3p, hsa-miR-373-5p, hsa-miR-4258, hsa-miR-4674, hsa-miR-3180, hsa-miR-6076, hsa-miR-1238-5p, hsa-miR-4463, hsa-miR-4486, hsa-miR-4730, hsa-miR-6766-3p, hsa-miR-4286, hsa-miR-6511a-5p, hsa-miR-4739, hsa-miR-6749-5p), its homologs, its transcription products, or and its variants or derivatives are included. Here, the gene, homolog, transcription product, variant, and derivative are as defined above.,
[0356] Preferred target nucleic acids are human genes containing the base sequences represented by any of SEQ ID NOs: 1 to 812, their transcripts, more preferably the said transcripts, namely miRNAs, their precursor RNAs, pri-miRNAs or pre-miRNAs.
[0357] The first target gene is the hsa-miR-6784-5p gene, their homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0358] The second target gene is the hsa-miR-1181 gene, their homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0359] The third target gene is the hsa-miR-671-5p gene, their homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0360] The fourth target gene is the hsa-miR-6857-5p gene, their homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0361] The fifth target gene is the hsa-miR-4276 gene, their homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0362] The sixth target gene is the hsa-miR-1914-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0363] The seventh target gene is the hsa-miR-149-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0364] The eighth target gene is the hsa-miR-937-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0365] The ninth target gene is the hsa-miR-4675 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0366] The tenth target gene is the hsa-miR-6795-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0367] The eleventh target gene is the hsa-miR-4731-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0368] The 12th target gene is the hsa-miR-5090 gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0369] The 13th target gene is the hsa-miR-3620-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0370] The 14th target gene is the hsa-miR-1343-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0371] The 15th target gene is the hsa-miR-6717-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0372] The 16th target gene is the hsa-miR-6825-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0373] The 17th target gene is the hsa-miR-6738-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0374] The 18th target gene is the hsa-miR-6769a-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0375] The 19th target gene is the hsa-miR-4728-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0376] The 20th target gene is the hsa-miR-652-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0377] The 21st target gene is the hsa-miR-4257 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0378] The 22nd target gene is the hsa-miR-6785-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0379] The 23rd target gene is the hsa-miR-7110-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0380] The 24th target gene is the hsa-miR-6887-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0381] The 25th target gene is the hsa-miR-887-3p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0382] The 26th target gene is the hsa-miR-1228-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0383] The 27th target gene is the hsa-miR-5572 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0384] The 28th target gene is the hsa-miR-6782-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0385] The 29th target gene is the hsa-miR-4298 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0386] The 30th target gene is the hsa-miR-6786-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0387] The 31st target gene is the hsa-miR-5010-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0388] The 32nd target gene is the hsa-miR-6087 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0389] The 33rd target gene is the hsa-miR-6765-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0390] The 34th target gene is the hsa-miR-6732-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0391] The 35th target gene is the hsa-miR-6787-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0392] The 36th target gene is the hsa-miR-6737-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0393] The 37th target gene is the hsa-miR-128-2-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0394] The 38th target gene is the hsa-miR-4270 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0395] The 39th target gene is the hsa-miR-6861-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0396] The 40th target gene is the hsa-miR-6756-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0397] The 41st target gene is the hsa-miR-1229-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0398] The 42nd target gene is the hsa-miR-6891-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0399] The 43rd target gene is the hsa-miR-6848-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0400] The 44th target gene is the hsa-miR-1237-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0401] The 45th target gene is the hsa-miR-30c-1-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0402] The 46th target gene is the hsa-miR-1233-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0403] The 47th target gene is the hsa-miR-211-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0404] The 48th target gene is the hsa-miR-4758-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0405] The 49th target gene is the hsa-miR-614 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0406] The 50th target gene is the hsa-miR-6746-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0407] The 51st target gene is the hsa-miR-1915-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0408] The 52nd target gene is the hsa-miR-4688 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0409] The 53rd target gene is the hsa-miR-3917 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of the gene or its transcript can serve as a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0410] The 54th target gene is the hsa-miR-5787 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0411] The 55th target gene is the hsa-miR-4632-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0412] The 56th target gene is the hsa-miR-6126 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0413] The 57th target gene is the hsa-miR-135a-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0414] The 58th target gene is the hsa-miR-8063 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0415] The 59th target gene is the hsa-miR-5698 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0416] The 60th target gene is the hsa-miR-6089 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0417] The 61st target gene is the hsa-miR-498 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0418] The 62nd target gene is the hsa-miR-296-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0419] The 63rd target gene is the hsa-miR-4419b gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0420] The 64th target gene is the hsa-miR-6802-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0421] The 65th target gene is the hsa-miR-6829-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0422] The 66th target gene is the hsa-miR-6803-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0423] The 67th target gene is the hsa-miR-1199-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0424] The 68th target gene is the hsa-miR-6840-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0425] The 69th target gene is the hsa-miR-6752-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0426] The 70th target gene is the hsa-miR-6798-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0427] The 71st target gene is the hsa-miR-6131 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0428] The 72nd target gene is the hsa-miR-4667-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0429] The 73rd target gene is the hsa-miR-6510-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0430] The 74th target gene is the hsa-miR-4690-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0431] The 75th target gene is the hsa-miR-920 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0432] The 76th target gene is the hsa-miR-23b-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0433] The 77th target gene is the hsa-miR-4448 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0434] The 78th target gene is the hsa-miR-2110 gene, its homologs, its transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0435] The 79th target gene is the hsa-miR-4706 gene, its homologs, its transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0436] The 80th target gene is the hsa-miR-7845-5p gene, its homologs, its transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0437] The 81st target gene is the hsa-miR-6808-5p gene, its homologs, its transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0438] The 82nd target gene is the hsa-miR-4447 gene, its homologs, its transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0439] The 83rd target gene is the hsa-miR-6869-5p gene, its homologs, its transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of the gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0440] The 84th target gene is the hsa-miR-1908-5p gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0441] The 85th target gene is the hsa-miR-6729-5p gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0442] The 86th target gene is the hsa-miR-5195-3p gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0443] The 87th target gene is the hsa-miR-638 gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Non-Patent Document 5 above).
[0444] The 88th target gene is the hsa-miR-6125 gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0445] The 89th target gene is the hsa-miR-3178 gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0446] The 90th target gene is the hsa-miR-3196 gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0447] The 91st target gene is the hsa-miR-8069 gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0448] The 92nd target gene is the hsa-miR-4723-5p gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0449] The 93rd target gene is the hsa-miR-4746-3p gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0450] The 94th target gene is the hsa-miR-4689 gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0451] The 95th target gene is the hsa-miR-6816-5p gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0452] The 96th target gene is the hsa-miR-6757-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0453] The 97th target gene is the hsa-miR-7109-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0454] The 98th target gene is the hsa-miR-6724-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0455] The 99th target gene is the hsa-miR-1225-3p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Non-Patent Document 5 above).
[0456] The 100th target gene is the hsa-miR-6875-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0457] The 101st target gene is the hsa-miR-7108-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0458] The 102nd target gene is the hsa-miR-4508 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0459] The 103rd target gene is the hsa-miR-6085 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0460] The 104th target gene is the hsa-miR-6779-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0461] The 105th target gene is the hsa-miR-642a-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0462] The 106th target gene is the hsa-miR-4695-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0463] The 107th target gene is the hsa-miR-7847-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0464] The 108th target gene is the hsa-miR-3197 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Non-Patent Document 5 above).
[0465] The 109th target gene is the hsa-miR-6769b-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0466] The 110th target gene is the hsa-miR-7641 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0467] The 111th target gene is the hsa-miR-187-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0468] The 112th target gene is the hsa-miR-3185 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0469] The 113th target gene is the hsa-miR-2861 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0470] The 114th target gene is the hsa-miR-3940-5p gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0471] The 115th target gene is the hsa-miR-1203 gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0472] The 116th target gene is the hsa-miR-615-5p gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0473] The 117th target gene is the hsa-miR-4787-5p gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Non-Patent Document 5 above).
[0474] The 118th target gene is the hsa-miR-1343-3p gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0475] The 119th target gene is the hsa-miR-6813-5p gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0476] The 120th target gene is the hsa-miR-1225-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0477] The 121st target gene is the hsa-miR-602 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0478] The 122nd target gene is the hsa-miR-4488 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0479] The 123rd target gene is the hsa-miR-125a-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0480] The 124th target gene is the hsa-miR-5100 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0481] The 125th target gene is the hsa-miR-4294 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0482] The 126th target gene is the hsa-miR-1231 gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of the gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0483] The 127th target gene is the hsa-miR-6765-3p gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of the gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0484] The 128th target gene is the hsa-miR-4442 gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of the gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0485] The 129th target gene is the hsa-miR-718 gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of the gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0486] The 130th target gene is the hsa-miR-6780b-5p gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of the gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0487] The 131st target gene is the hsa-miR-6090 gene, its homologs, its transcripts, or its variants or derivatives. Reports have been known so far that changes in the expression of the gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0488] The 132nd target gene is the hsa-miR-6845-5p gene, its homologs, their transcripts, or their variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0489] The 133rd target gene is the hsa-miR-4741 gene, its homologs, their transcripts, or their variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0490] The 134th target gene is the hsa-miR-4467 gene, its homologs, their transcripts, or their variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0491] The 135th target gene is the hsa-miR-4707-5p gene, its homologs, their transcripts, or their variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0492] The 136th target gene is the hsa-miR-4271 gene, its homologs, their transcripts, or their variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0493] The 137th target gene is the hsa-miR-4673 gene, its homologs, their transcripts, or their variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0494] The 138th target gene is the hsa-miR-3184-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0495] The 139th target gene is the hsa-miR-1469 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0496] The 140th target gene is the hsa-miR-4640-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0497] The 141st target gene is the hsa-miR-663a gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0498] The 142nd target gene is the hsa-miR-6791-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0499] The 143rd target gene is the hsa-miR-6826-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0500] The 144th target gene is the hsa-miR-4433b-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0501] The 145th target gene is the hsa-miR-1915-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0502] The 146th target gene is the hsa-miR-4417 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0503] The 147th target gene is the hsa-miR-4449 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0504] The 148th target gene is the hsa-miR-4707-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0505] The 149th target gene is the hsa-miR-3180-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0506] The 150th target gene is the hsa-miR-5585-3p gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0507] The 151st target gene is the hsa-miR-1268a gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for early pancreatic cancer or pancreatic cancer precursor lesions (Patent Document 4 above).
[0508] The 152nd target gene is the hsa-miR-8072 gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0509] The 153rd target gene is the hsa-miR-296-5p gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for early pancreatic cancer or pancreatic cancer precursor lesions (Patent Document 5 above).
[0510] The 154th target gene is the hsa-miR-204-3p gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0511] The 155th target gene is the hsa-miR-4454 gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0512] The 156th target gene is the hsa-miR-6722-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0513] The 157th target gene is the hsa-miR-1290 gene, its homologs, their transcripts, or their mutants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0514] The 158th target gene is the hsa-miR-3622a-5p gene, its homologs, their transcripts, or their mutants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0515] The 159th target gene is the hsa-miR-939-5p gene, its homologs, their transcripts, or their mutants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for early pancreatic cancer or pancreatic cancer precursor lesions (Patent Document 4 above).
[0516] The 160th target gene is the hsa-miR-675-5p gene, its homologs, their transcripts, or their mutants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Non-Patent Document 5 above).
[0517] The 161st target gene is the hsa-miR-3131 gene, its homologs, their transcripts, or their mutants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0518] The 162nd target gene is the hsa-miR-4648 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0519] The 163rd target gene is the hsa-miR-1268b gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0520] The 164th target gene is the hsa-miR-6741-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0521] The 165th target gene is the hsa-miR-6893-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0522] The 166th target gene is the hsa-miR-3162-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0523] The 167th target gene is the hsa-miR-642b-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for early pancreatic cancer or pancreatic cancer precursor lesions (Patent Document 4 above).
[0524] The 168th target gene is the hsa-miR-4734 gene, its homologs, its transcripts, or their variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0525] The 169th target gene is the hsa-miR-150-3p gene, its homologs, its transcripts, or their variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0526] The 170th target gene is the hsa-miR-8089 gene, its homologs, its transcripts, or their variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0527] The 171st target gene is the hsa-miR-6805-3p gene, its homologs, its transcripts, or their variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0528] The 172nd target gene is the hsa-miR-7113-3p gene, its homologs, its transcripts, or their variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0529] The 173rd target gene is the hsa-miR-6850-5p gene, its homologs, its transcripts, or their variants or derivatives. Reports have been known so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0530] The 174th target gene is the hsa-miR-6799-5p gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0531] The 175th target gene is the hsa-miR-6768-5p gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0532] The 176th target gene is the hsa-miR-92b-5p gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0533] The 177th target gene is the hsa-miR-3679-5p gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Non-Patent Document 5 above).
[0534] The 178th target gene is the hsa-miR-4792 gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0535] The 179th target gene is the hsa-miR-3656 gene, its homologs, their transcripts, or their mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0536] The 180th target gene is the hsa-miR-92a-2-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0537] The 181st target gene is the hsa-miR-4466 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0538] The 182nd target gene is the hsa-miR-4513 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0539] The 183rd target gene is the hsa-miR-6781-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0540] The 184th target gene is the hsa-miR-4649-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0541] The 185th target gene is the hsa-miR-6775-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0542] The 186th target gene is the hsa-miR-4651 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0543] The 187th target gene is the hsa-miR-3195 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0544] The 188th target gene is the hsa-miR-6726-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0545] The 189th target gene is the hsa-miR-6872-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0546] The 190th target gene is the hsa-miR-371a-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0547] The 191st target gene is the hsa-miR-6777-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0548] The 192nd target gene is the hsa-miR-6789-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0549] The 193rd target gene is the hsa-miR-7975 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0550] The 194th target gene is the hsa-miR-6821-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0551] The 195th target gene is the hsa-miR-4534 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0552] The 196th target gene is the hsa-miR-619-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0553] The 197th target gene is the hsa-miR-7107-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0554] The 198th target gene is the hsa-miR-1228-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0555] The 199th target gene is the hsa-miR-6774-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0556] The 200th target gene is the hsa-miR-6805-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0557] The 201st target gene is the hsa-miR-23a-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 3 above).
[0558] The 202nd target gene is the hsa-miR-4665-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0559] The 203rd target gene is the hsa-miR-4505 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0560] The 204th target gene is the hsa-miR-4638-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0561] The 205th target gene is the hsa-miR-24-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0562] The 206th target gene is the hsa-miR-3135b gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0563] The 207th target gene is the hsa-miR-4745-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0564] The 208th target gene is the hsa-miR-128-1-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0565] The 209th target gene is the hsa-miR-4476 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0566] The 210th target gene is the hsa-miR-4687-3p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0567] The 211th target gene is the hsa-miR-3665 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Non-Patent Document 5 above).
[0568] The 212th target gene is the hsa-miR-6806-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Patent Document 2 above).
[0569] The 213th target gene is the hsa-miR-3937 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Non-Patent Document 5 above).
[0570] The 214th target gene is the hsa-miR-711 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Non-Patent Document 5 above).
[0571] The 215th target gene is the hsa-miR-3141 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for pancreatic cancer (Non-Patent Document 5 above).
[0572] The target gene of No. 216 is the hsa-miR-3188 gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0573] The target gene of No. 217 is the hsa-miR-4281 gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0574] The target gene of No. 218 is the hsa-miR-5196-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0575] The target gene of No. 219 is the hsa-miR-6880-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0576] The target gene of No. 220 is the hsa-miR-3960 gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0577] The target gene of No. 221 is the hsa-miR-3648 gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 1 above).
[0578] The target gene of No. 222 is the hsa-miR-6721-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0579] The target gene of No. 223 is the hsa-miR-4492 gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0580] The target gene of No. 224 is the hsa-miR-744-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0581] The target gene of No. 225 is the hsa-miR-7704 gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Patent Document 2 above).
[0582] The target gene of No. 226 is the hsa-miR-4749-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0583] The target gene of No. 227 is the hsa-miR-6794-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there have been no reports that changes in the expression of genes or their transcripts can be markers for pancreatic cancer.
[0584] The target gene of No. 228 is the hsa-miR-6511a-5p gene, its homologs, its transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer.
[0585] The target gene of No. 229 is the hsa-miR-6824-5p gene, its homologs, its transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer.
[0586] The target gene of No. 230 is the hsa-miR-762 gene, its homologs, its transcripts, or their variants or derivatives. There has been a report so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Non-Patent Document 5 above).
[0587] The target gene of No. 231 is the hsa-miR-6836-3p gene, its homologs, its transcripts, or their variants or derivatives. There has been a report so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0588] The target gene of No. 232 is the hsa-miR-6727-5p gene, its homologs, its transcripts, or their variants or derivatives. There has been a report so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0589] The target gene of No. 233 is the hsa-miR-4739 gene, its homologs, its transcripts, or their variants or derivatives. There has been a report so far that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Non-Patent Document 5 above).
[0590] The 234th target gene is the hsa-miR-7977 gene, its homologs, its transcripts, or its mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0591] The 235th target gene is the hsa-miR-4484 gene, its homologs, its transcripts, or its mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0592] The 236th target gene is the hsa-miR-6515-3p gene, its homologs, its transcripts, or its mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0593] The 237th target gene is the hsa-miR-373-5p gene, its homologs, its transcripts, or its mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Non-Patent Document 5 above).
[0594] The 238th target gene is the hsa-miR-4258 gene, its homologs, its transcripts, or its mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0595] The 239th target gene is the hsa-miR-4674 gene, its homologs, its transcripts, or its mutants or derivatives. So far, there have been reports that changes in the expression of a gene or its transcript can be markers for pancreatic cancer (Patent Document 2 above).
[0596] The 240th target gene is the hsa-miR-3180 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Non-Patent Document 5 above).
[0597] The 241st target gene is the hsa-miR-6076 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0598] The 242nd target gene is the hsa-miR-1238-5p gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0599] The 243rd target gene is the hsa-miR-4463 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Non-Patent Document 5 above).
[0600] The 244th target gene is the hsa-miR-4486 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Patent Document 2 above).
[0601] The 245th target gene is the hsa-miR-4730 gene, its homologs, its transcripts, or its variants or derivatives. There have been reports that changes in the expression of a gene or its transcript can be a marker for pancreatic cancer (Non-Patent Document 5 above).
[0602] The 246th target gene is the hsa-miR-6766-3p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of a gene or its transcript can serve as a marker for pancreatic cancer.
[0603] The 247th target gene is the hsa-miR-4286 gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been a report that changes in the expression of a gene or its transcript can serve as a marker for pancreatic cancer (Patent Document 2 above).
[0604] The 248th target gene is the hsa-miR-6511a-5p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of a gene or its transcript can serve as a marker for pancreatic cancer.
[0605] The 249th target gene is the hsa-miR-4739 gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been a report that changes in the expression of a gene or its transcript can serve as a marker for pancreatic cancer (Non-Patent Document 5 above).
[0606] The 250th target gene is the hsa-miR-6749-5p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of a gene or its transcript can serve as a marker for pancreatic cancer.
[0607] 2. Nucleic Acid Probes or Primers for Detecting Early Pancreatic Cancer or Pancreatic Cancer Precursors In the present invention, a nucleic acid that can specifically bind to a target nucleic acid as the above-mentioned early pancreatic cancer or pancreatic cancer precursor marker can be used as a nucleic acid for detecting or diagnosing early pancreatic cancer or pancreatic cancer precursors, for example, a nucleic acid probe or primer.
[0608] In the present invention, nucleic acid probes or primers for detecting early pancreatic cancer or pancreatic cancer precursor lesions, or that can be used for diagnosing early pancreatic cancer or pancreatic cancer precursor lesions, are human-derived hsa-miR-6784-5p, hsa-miR-1181, hsa-miR-671-5p, hsa-miR-6857-5p, hsa-miR-4276, hsa-miR-1914-3p, hsa-miR-149-3p, hsa-miR-937-5p, hsa-miR-4675, hsa-miR-6795-5p, hsa-miR-4731-5p, hsa-miR-5090, hsa-miR-3620-5p, hsa-miR-1343-5p, hsa-miR-6717-5p, hsa-miR-6825-5p, hsa-miR-6738-5p, hsa-miR-6769a-5p, hsa-miR-4728-5p, hsa-miR-652-5p, hsa-miR-4257, hsa-miR-6785-5p, hsa-miR-7110-5p, hsa-miR-6887-5p, hsa-miR-887-3p, hsa-miR-1228-5p, hsa-miR-5572, hsa-miR-6782-5p, hsa-miR-4298, hsa-miR-6786-5p, hsa-miR-5010-5p, hsa-miR-6087, hsa-miR-6765-5p, hsa-miR-6732-5p, hsa-miR-6787-5p, hsa-miR-6737-5p, hsa-miR-128-2-5p, hsa-miR-4270, hsa-miR-6861-5p, hsa-miR-6756-5p, hsa-miR-1229-5p, hsa-miR-6891-5p, hsa-miR-6848-5p, hsa-miR-1237-5p, hsa-miR-30c-1-3p, hsa-miR-1233-5p, hsa-miR-211-3p, hsa-miR-4758-5p, hsa-miR-614, hsa-miR-6746-5p, hsa-miR-1915-5p, hsa-miR-4688, hsa-miR-3917, hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126, hsa-miR-135a-3p, hsa-miR-8063, hsa-miR-5698, as target nucleic acids for early pancreatic cancer or pancreatic cancer precursor lesions.hsa-miR-6089, hsa-miR-498, hsa-miR-296-3p, hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p, hsa-miR-6803-5p, hsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p, hsa-miR-6798-5p, hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p, hsa-miR-4690-5p, hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448, hsa-miR-2110, hsa-miR-4706, hsa-miR-7845-5p, hsa-miR-6808-5p, hsa-miR-4447, hsa-miR-6869-5p, hsa-miR-6794-5p, hsa-miR-6511a-5p, hsa-miR-6824-5p, hsa-miR-6766-3p, hsa-miR-6511a-5p, and hsa-miR-6749-5p, or combinations thereof, and hsa-miR-1908-5p, hsa-miR-6729-5p, hsa-miR-5195-3p, hsa-miR-638, hsa-miR-6125, hsa-miR-3178, hsa-miR-3196, hsa-miR-8069, hsa-miR-4723-5p, hsa-miR-4746-3p, hsa-miR-4689, hsa-miR-6816-5p, hsa-miR-6757-5p, hsa-miR-7109-5p, hsa-miR-6724-5p, hsa-miR-1225-3p, hsa-miR-6875-5p, hsa-miR-7108-5p, hsa-miR-4508, hsa-miR-6085, hsa-miR-6779-5p, hsa-miR-642a-3p, hsa-miR-4695-5p, hsa-miR-7847-3p, hsa-miR-3197, hsa-miR-6769b-5p, hsa-miR-7641, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-2861, hsa-miR-3940-5p, hsa-miR-1203, hsa-miR-615-5p, hsa-miR-4787-5phsa-miR-1343-3p, hsa-miR-6813-5p, hsa-miR-1225-5p, hsa-miR-602, hsa-miR-4488, hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294, hsa-miR-1231, hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718, hsa-miR-6780b-5p, hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741, hsa-miR-4467, hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673, hsa-miR-3184-5p, hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a, hsa-miR-6791-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p, hsa-miR-4417, hsa-miR-4449, hsa-miR-4707-3p, hsa-miR-3180-3p, hsa-miR-5585-3p, hsa-miR-1268a, hsa-miR-8072, hsa-miR-296-5p, hsa-miR-204-3p, hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290, hsa-miR-3622a-5p, hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131, hsa-miR-4648, hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p, hsa-miR-3162-5p, hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p, hsa-miR-8089, hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p, hsa-miR-6799-5p, hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p, hsa-miR-4792, hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466, hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5pThe presence, expression level or abundance of hsa-miR-4651, hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p, hsa-miR-371a-5p, hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975, hsa-miR-6821-5p, hsa-miR-4534, hsa-miR-619-5p, hsa-miR-7107-5p, hsa-miR-1228-3p, hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p, hsa-miR-4665-5p, hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p, hsa-miR-3135b, hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476, hsa-miR-4687-3p, hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937, hsa-miR-711, hsa-miR-3141, hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5p, hsa-miR-6880-5p, hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p, hsa-miR-4492, hsa-miR-744-5p, hsa-miR-7704, hsa-miR-4749-5p, hsa-miR-762, hsa-miR-6836-3p, hsa-miR-6727-5p, hsa-miR-4739, hsa-miR-7977, hsa-miR-4484, hsa-miR-6515-3p, hsa-miR-373-5p, hsa-miR-4258, hsa-miR-4674, hsa-miR-3180, hsa-miR-6076, hsa-miR-1238-5p, hsa-miR-4463, hsa-miR-4486, hsa-miR-4730, hsa-miR-4286, and hsa-miR-4739, or combinations thereof, homologs thereof, transcription products thereof, or variants or derivatives thereof can be qualitatively and / or quantitatively measured.
[0609] The above-mentioned target nucleic acids may have increased or decreased expression levels depending on the type of the target nucleic acid in a subject suffering from early-stage pancreatic cancer or a pancreatic cancer precursor lesion as compared to a healthy subject (hereinafter referred to as "increase / decrease"). For example, Table 2 illustrates the changes in the expression levels of target miRNAs corresponding to SEQ ID NOs: 1 to 226 in the blood (serum) of patients with pancreatic cancer precursor lesions (humans) relative to healthy subjects. As shown in Table 2, there are miRNAs with increased expression levels and, conversely, miRNAs with decreased expression levels depending on the type of the target miRNA. In the present invention, any of the target miRNAs selected this time and described in the specification can be used for detecting and determining early-stage pancreatic cancer or a pancreatic cancer precursor lesion in a subject.
[0610] Therefore, according to the present invention, the expression levels of the above-mentioned target nucleic acids are measured for body fluids derived from a subject (e.g., a human) suspected of suffering from early-stage pancreatic cancer or a pancreatic cancer precursor lesion and body fluids derived from a healthy subject, and they are compared, so that it can be effectively used for detecting early-stage pancreatic cancer or a pancreatic cancer precursor lesion with high accuracy. Further, according to the present invention, the expression levels of the above-mentioned target nucleic acids are measured for body fluids derived from a subject (e.g., a human) suspected of suffering from early-stage pancreatic cancer or a pancreatic cancer precursor lesion and body fluids derived from a patient with advanced pancreatic cancer, a patient with biliary tract cancer, a patient with breast cancer, a patient with prostate cancer, a patient with colorectal cancer, a patient with gastric cancer, a patient with esophageal cancer, a patient with liver cancer, a patient with a pancreatic benign disease, a patient with a prostate benign disease, or a combination thereof, and they are compared, so that it can be effectively used for specifically and accurately identifying early-stage pancreatic cancer or a pancreatic cancer precursor lesion from other cancers and benign diseases.
[0611] The nucleic acid probe or primer that can be used in the present invention is a nucleic acid probe that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one, at least two, at least three, at least four, or at least five of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, or a primer for amplifying a polynucleotide consisting of a base sequence represented by at least one, at least two, at least three, at least four, or at least five of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250.
[0612] The nucleic acid probes or primers that can be used in the present invention further include nucleic acid probes that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one, at least two, at least three, at least four, or at least five of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249, or primers for amplifying a polynucleotide consisting of a base sequence represented by at least one, at least two, at least three, at least four, or at least five of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249.
[0613] Specifically, the above-mentioned nucleic acid probes or primers include a polynucleotide group consisting of a base sequence represented by any of SEQ ID NOs: 1 to 250 or a base sequence in which u is t in the base sequence, and its complementary polynucleotide group, a polynucleotide group that hybridizes with DNA consisting of a base sequence complementary to the base sequence under stringent conditions (described later) and its complementary polynucleotide group, and one or a combination of a plurality of polynucleotides selected from a polynucleotide group containing 15 or more, preferably 17 or more consecutive bases in the base sequence of these polynucleotide groups. In this regard, the target miRNAs used in the present invention also include precursor miRNAs such as those shown by SEQ ID NOs: 251 to 518 in Table 1, and isomiRNAs such as those shown by SEQ ID NOs: 519 to 812. IsomiRNAs include those with a short base number of about 15, those with a long base number of about 29, and those with mutations such as substitutions. Therefore, in the present invention, the above-mentioned nucleic acid probes or primers also include nucleic acid probes or primers for enabling measurement of the expression of precursor miRNAs and target isomiRNAs. These polynucleotides can be used as nucleic acid probes and primers for detecting the above-mentioned early pancreatic cancer or pancreatic cancer precursor lesion markers that are target nucleic acids.
[0614] More specifically, examples of the nucleic acid probes or primers that can be used in the present invention are at least one (i.e., one or more) polynucleotides selected from the group consisting of the following polynucleotides (a) to (e). (a) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (b) A polynucleotide containing a base sequence represented by any of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, (c) A polynucleotide consisting of a base sequence complementary to a base sequence represented by any of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (d) A polynucleotide containing a base sequence complementary to a base sequence represented by any of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, or a base sequence in which u is t in the base sequence, and (e) A polynucleotide that hybridizes under stringent conditions with any of the polynucleotides (a) to (d).
[0615] The nucleic acid probes or primers that can be used in the present invention can further contain, in addition to at least one (i.e., one or more) polynucleotides selected from any of the above polynucleotides (a) to (e), at least one (i.e., one or more) polynucleotides shown in any of the following (f) to (j). (f) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249, or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (g) A polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249, (h) A polynucleotide consisting of a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249, or a base sequence in which u is t in the base sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (i) A polynucleotide containing a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249, or a base sequence in which u is t in the base sequence, and (j) A polynucleotide that hybridizes with any of the polynucleotides of (f) to (i) under stringent conditions.
[0616] In the above polynucleotide, the "fragment thereof containing 15 or more consecutive bases" can include, for example, the number of bases in the range of 15 consecutive bases to less than the total number of bases in the sequence, 17 consecutive bases to less than the total number of bases in the sequence, 19 consecutive bases to less than the total number of bases in the sequence, etc. in the base sequence of each polynucleotide, but is not limited thereto.
[0617] Any of the above polynucleotides or fragments thereof used in the present invention may be DNA or RNA.
[0618] The above polynucleotides that can be used in the present invention can be prepared using general techniques such as DNA recombination techniques, PCR methods, and methods using DNA / RNA automatic synthesizers.
[0619] DNA recombination technology and PCR method can use the techniques described in, for example, Ausubel et al., Current Protocols in Molecular Biology, John Willey & Sons, US (1993); Sambrook et al., Molecular Cloning A Laboratory Manual, Cold Spring Harbor Laboratory Press, US (1989).
[0620] Human-derived hsa-miR-6784-5p, hsa-miR-1181, hsa-miR-671-5p, hsa-miR-6857-5p, hsa-miR-4276, hsa-miR-1914-3p, hsa-miR-149-3p, hsa-miR-937-5p, hsa-miR-4675, hsa-miR-6795-5p, hsa-miR-4731-5p, hsa-miR-5090, hsa-miR-3620-5p, hsa-miR-1343-5p, hsa-miR-6717-5p, hsa-miR-6825-5p, hsa-miR-6738-5p, hsa-miR-6769a-5p, hsa-miR-4728-5p, hsa-miR-652-5p, hsa-miR-4257, hsa-miR-6785-5p, hsa-miR-7110-5p, hsa-miR-6887-5p, hsa-miR-887-3p, hsa-miR-1228-5p, hsa-miR-5572, hsa-miR-6782-5p, hsa-miR-4298, hsa-miR-6786-5p, hsa-miR-5010-5p, hsa-miR-6087, hsa-miR-6765-5p, hsa-miR-6732-5p, hsa-miR-6787-5p, hsa-miR-6737-5p, hsa-miR-128-2-5p, hsa-miR-4270, hsa-miR-6861-5p, hsa-miR-6756-5p, hsa-miR-1229-5p, hsa-miR-6891-5p, hsa-miR-6848-5p, hsa-miR-1237-5p, hsa-miR-30c-1-3p, hsa-miR-1233-5p, hsa-miR-211-3p, hsa-miR-4758-5p, hsa-miR-614, hsa-miR-6746-5p, hsa-miR-1915-5p, hsa-miR-4688, hsa-miR-3917, hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126, hsa-miR-135a-3p, hsa-miR-8063, hsa-miR-5698, hsa-miR-6089, hsa-miR-498, hsa-miR-296-3p, hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p, represented by Array Numbers 1 to 250hsa-miR-6803-5p, hsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p, hsa-miR-6798-5p, hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p, hsa-miR-4690-5p, hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448, hsa-miR-2110, hsa-miR-4706, hsa-miR-7845-5p, hsa-miR-6808-5p, hsa-miR-4447, hsa-miR-6869-5p, hsa-miR-1908-5p, hsa-miR-6729-5p, hsa-miR-5195-3p, hsa-miR-638, hsa-miR-6125, hsa-miR-3178, hsa-miR-3196, hsa-miR-8069, hsa-miR-4723-5p, hsa-miR-4746-3p, hsa-miR-4689, hsa-miR-6816-5p, hsa-miR-6757-5p, hsa-miR-7109-5p, hsa-miR-6724-5p, hsa-miR-1225-3p, hsa-miR-6875-5p, hsa-miR-7108-5p, hsa-miR-4508, hsa-miR-6085, hsa-miR-6779-5p, hsa-miR-642a-3p, hsa-miR-4695-5p, hsa-miR-7847-3p, hsa-miR-3197, hsa-miR-6769b-5p, hsa-miR-7641, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-2861, hsa-miR-3940-5p, hsa-miR-1203, hsa-miR-615-5p, hsa-miR-4787-5p, hsa-miR-1343-3p, hsa-miR-6813-5p, hsa-miR-1225-5p, hsa-miR-602, hsa-miR-4488, hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294, hsa-miR-1231, hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718, hsa-miR-6780b-5p, hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741hsa-miR-4467, hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673, hsa-miR-3184-5p, hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a, hsa-miR-6791-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p, hsa-miR-4417, hsa-miR-4449, hsa-miR-4707-3p, hsa-miR-3180-3p, hsa-miR-5585-3p, hsa-miR-1268a, hsa-miR-8072, hsa-miR-296-5p, hsa-miR-204-3p, hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290, hsa-miR-3622a-5p, hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131, hsa-miR-4648, hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p, hsa-miR-3162-5p, hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p, hsa-miR-8089, hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p, hsa-miR-6799-5p, hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p, hsa-miR-4792, hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466, hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5p, hsa-miR-4651, hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p, hsa-miR-371a-5p, hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975, hsa-miR-6821-5p, hsa-miR-4534, hsa-miR-619-5p, hsa-miR-7107-5p, hsa-miR-1228-3p, hsa-miR-6774-5p, hsa-miR-6805-5phsa-miR-23a-3p, hsa-miR-4665-5p, hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p, hsa-miR-3135b, hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476, hsa-miR-4687-3p, hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937, hsa-miR-711, hsa-miR-3141, hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5p, hsa-miR-6880-5p, hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p, hsa-miR-4492, hsa-miR-744-5p, hsa-miR-7704, hsa-miR-4749-5p, hsa-miR-6794-5p, hsa-miR-6511a-5p, hsa-miR-6824-5p, hsa-miR-762, hsa-miR-6836-3p, hsa-miR-6727-5p, hsa-miR-4739, hsa-miR-7977, hsa-miR-4484, hsa-miR-6515-3p, hsa-miR-373-5p, hsa-miR-4258, hsa-miR-4674, hsa-miR-3180, hsa-miR-6076, hsa-miR-1238-5p, hsa-miR-4463, hsa-miR-4486, hsa-miR-4730, hsa-miR-6766-3p, hsa-miR-4286, hsa-miR-6511a-5p, hsa-miR-4739, and hsa-miR-6749-5p are known, and their acquisition methods are also known as described above. Therefore, by cloning this gene, a polynucleotide can be prepared as a nucleic acid probe or primer usable in the present invention.,
[0621] Such nucleic acid probes or primers can be chemically synthesized using a DNA automatic synthesizer. Generally, the phosphoramidite method is used for this synthesis, and single-stranded DNA up to about 100 bases can be automatically synthesized by this method. DNA automatic synthesizers are commercially available from, for example, Polygen, ABI, Applied BioSystems, etc.
[0622] Alternatively, the polynucleotide of the present invention can also be prepared by a cDNA cloning method. For cDNA cloning technology, for example, microRNA Cloning Kit Wako can be used.
[0623] Here, the sequences of the nucleic acid probes and primers for detecting the polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 1 to 250 do not exist in vivo as miRNA or its precursor. For example, the base sequences represented by SEQ ID NO: 14 and SEQ ID NO: 118 are generated from the precursor represented by SEQ ID NO: 264, but this precursor has a hairpin-like structure as shown in FIG. 1, and the base sequences represented by SEQ ID NO: 14 and SEQ ID NO: 118 have mismatched sequences with each other. Therefore, a completely complementary base sequence to the base sequence represented by SEQ ID NO: 14 or SEQ ID NO: 118 is not naturally generated in vivo. Therefore, the nucleic acid probes and primers for detecting the base sequence represented by any of SEQ ID NOs: 1 to 250 will have artificial base sequences that do not exist in vivo.
[0624] 3. Kit or device for detecting early pancreatic cancer or pancreatic cancer precursor lesions The present invention also provides a kit or device for detecting early pancreatic cancer or pancreatic cancer precursor lesions, which contains one or more of the polynucleotides (which may include variants, fragments, or derivatives) that can be used as nucleic acid probes or primers in the present invention for measuring the target nucleic acid that is a marker for early pancreatic cancer or pancreatic cancer precursor lesions.
[0625] The target nucleic acid, which is a marker for early pancreatic cancer or pancreatic cancer precursor lesions in the present invention, is at least one nucleic acid selected from the following Group A.
[0626] Group A: hsa-miR-6784-5p, hsa-miR-1181, hsa-miR-671-5p, hsa-miR-6857-5p, hsa-miR-4276, hsa-miR-1914-3p, hsa-miR-149-3p, hsa-miR-937-5p, hsa-miR-4675, hsa-miR-6795-5p, hsa-miR-4731-5p, hsa-miR-5090, hsa-miR-3620-5p, hsa-miR-1343-5p, hsa-miR-6717-5p, hsa-miR-6825-5p, hsa-miR-6738-5p, hsa-miR-6769a-5p, hsa-miR-4728-5p, hsa-miR-652-5p, hsa-miR-4257, hsa-miR-6785-5p, hsa-miR-7110-5p, hsa-miR-6887-5p, hsa-miR-887-3p, hsa-miR-1228-5p, hsa-miR-5572, hsa-miR-6782-5p, hsa-miR-4298, hsa-miR-6786-5p, hsa-miR-5010-5p, hsa-miR-6087, hsa-miR-6765-5p, hsa-miR-6732-5p, hsa-miR-6787-5p, hsa-miR-6737-5p, hsa-miR-128-2-5p, hsa-miR-4270, hsa-miR-6861-5p, hsa-miR-6756-5p, hsa-miR-1229-5p, hsa-miR-6891-5p, hsa-miR-6848-5p, hsa-miR-1237-5p, hsa-miR-30c-1-3p, hsa-miR-1233-5p, hsa-miR-211-3p, hsa-miR-4758-5p, hsa-miR-614, hsa-miR-6746-5p, hsa-miR-1915-5p, hsa-miR-4688, hsa-miR-3917, hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126, hsa-miR-135a-3p, hsa-miR-8063, hsa-miR-5698, hsa-miR-6089, hsa-miR-498, hsa-miR-296-3p, hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p, hsa-miR-6803-5phsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p, hsa-miR-6798-5p, hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p, hsa-miR-4690-5p, hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448, hsa-miR-2110, hsa-miR-4706, hsa-miR-7845-5p, hsa-miR-6808-5p, hsa-miR-4447, hsa-miR-6869-5p, hsa-miR-6794-5p, hsa-miR-6511a-5p, hsa-miR-6824-5p, hsa-miR-6766-3p, hsa-miR-6511a-5p, and hsa-miR-6749-5p.,
[0627] Additional target nucleic acids that may optionally be used for measurement are at least one nucleic acid selected from the following Group B.
[0628] Group B: hsa-miR-1908-5p, hsa-miR-6729-5p, hsa-miR-5195-3p, hsa-miR-638, hsa-miR-6125, hsa-miR-3178, hsa-miR-3196, hsa-miR-8069, hsa-miR-4723-5p, hsa-miR-4746-3p, hsa-miR-4689, hsa-miR-6816-5p, hsa-miR-6757-5p, hsa-miR-7109-5p, hsa-miR-6724-5p, hsa-miR-1225-3p, hsa-miR-6875-5p, hsa-miR-7108-5p, hsa-miR-4508, hsa-miR-6085, hsa-miR-6779-5p, hsa-miR-642a-3p, hsa-miR-4695-5p, hsa-miR-7847-3p, hsa-miR-3197, hsa-miR-6769b-5p, hsa-miR-7641, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-2861, hsa-miR-3940-5p, hsa-miR-1203, hsa-miR-615-5p, hsa-miR-4787-5p, hsa-miR-1343-3p, hsa-miR-6813-5p, hsa-miR-1225-5p, hsa-miR-602, hsa-miR-4488, hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294, hsa-miR-1231, hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718, hsa-miR-6780b-5p, hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741, hsa-miR-4467, hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673, hsa-miR-3184-5p, hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a, hsa-miR-6791-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p, hsa-miR-4417, hsa-miR-4449, hsa-miR-4707-3p, hsa-miR-3180-3p, hsa-miR-5585-3p, hsa-miR-1268ahsa-miR-8072, hsa-miR-296-5p, hsa-miR-204-3p, hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290, hsa-miR-3622a-5p, hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131, hsa-miR-4648, hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p, hsa-miR-3162-5p, hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p, hsa-miR-8089, hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p, hsa-miR-6799-5p, hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p, hsa-miR-4792, hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466, hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5p, hsa-miR-4651, hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p, hsa-miR-371a-5p, hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975, hsa-miR-6821-5p, hsa-miR-4534, hsa-miR-619-5p, hsa-miR-7107-5p, hsa-miR-1228-3p, hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p, hsa-miR-4665-5p, hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p, hsa-miR-3135b, hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476, hsa-miR-4687-3p, hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937, hsa-miR-711, hsa-miR-3141, hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5phsa-miR-6880-5p, hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p, hsa-miR-4492, hsa-miR-744-5p, hsa-miR-7704, hsa-miR-4749-5p, hsa-miR-762, hsa-miR-6836-3p, hsa-miR-6727-5p, hsa-miR-4739, hsa-miR-7977, hsa-miR-4484, hsa-miR-6515-3p, hsa-miR-373-5p, hsa-miR-4258, hsa-miR-4674, hsa-miR-3180, hsa-miR-6076, hsa-miR-1238-5p, hsa-miR-4463, hsa-miR-4486, hsa-miR-4730, hsa-miR-4286, and hsa-miR-4739.
[0629] The kit or device of the...
Claims
1. A kit for detecting early pancreatic cancer or a pancreatic cancer precursor lesion, comprising a nucleic acid probe that can specifically bind to a polynucleotide of miR-4632-5p, which is a marker for early pancreatic cancer or a pancreatic cancer precursor lesion, and / or a primer that specifically recognizes and amplifies the polynucleotide.
2. The nucleic acid probe and / or primer is a polynucleotide selected from the group consisting of the following polynucleotides (a) to (e): (a) A polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 55 or a nucleotide sequence in which u is t in the nucleotide sequence, or a fragment thereof containing 19 or more consecutive bases, (b) A polynucleotide containing the nucleotide sequence represented by SEQ ID NO: 55, (c) A polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence represented by SEQ ID NO: 55 or a nucleotide sequence in which u is t in the nucleotide sequence, or a fragment thereof containing 19 or more consecutive bases, (d) A polynucleotide containing a nucleotide sequence complementary to the nucleotide sequence represented by SEQ ID NO: 55 or a nucleotide sequence in which u is t in the nucleotide sequence, and (e) A polynucleotide that hybridizes with any of the polynucleotides (a) to (d) under stringent conditions. The kit according to claim 1, which is a polynucleotide selected from the group consisting of the above.
3. The kit is miR-6784-5p, miR-1181, miR-671-5p, miR-6857-5p, miR-4276, miR-1914-3p, miR-149-3p, miR-937-5p, miR-4675, miR-6795-5p, miR-4731-5p, miR-5090, miR-3620-5p, miR-6717-5p, miR-6825-5p, miR-6738-5p, miR-6769a-5p, miR-4728-5p, miR-652-5p, miR-4257, miR-7110-5p, miR-6887-5p, miR-887-3p, miR-1228-5p, miR-5572, miR-6782-5p, miR-4298, miR-6786-5p, miR-5010-5p, miR-6087, miR-6765-5p, miR-6732-5p, miR-6787-5p, miR-6737-5p, miR-128-2-5p, miR-4270, miR-6861-5p, miR-6756-5p, miR-1229-5p, miR-6891-5p, miR-6848-5p, miR-1237-5p, miR-30c-1-3p, miR-1233-5p, miR-211-3p, miR-4758-5p, miR-614, miR-6746-5p, miR-1915-5p, miR-4688, miR-3917, miR-5787, miR-6126, miR-135a-3p, miR-8063, miR-5698, miR-6089, miR-498, miR-296-3p, miR-4419b, miR-6802-5p, miR-6829-5p, miR-6803-5p, miR-1199-5p, miR-6840-3p, miR-6752-5p, miR-6798-5p, miR-6131, miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920, miR-23b-3p, miR-4448, miR-2110, miR-4706, miR-7845-5p, miR-6808-5p, miR-4447, miR-6869-5p, miR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125, miR-3178, miR-3196, miR-8069, miR-4723-5p, which is another early pancreatic cancer or pancreatic cancer precursor lesion marker.miR-4746-3p, miR-4689, miR-6816-5p, miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p, miR-6875-5p, miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p, miR-4695-5p, miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p, miR-3185, miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p, miR-1343-3p, miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p, miR-5100, miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718, miR-6780b-5p, miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p, miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a, miR-6791-5p, miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449, miR-4707-3p, miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p, miR-204-3p, miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p, miR-675-5p, miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p, miR-3162-5p, miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p, miR-7113-3p, miR-6850-5p, miR-6799-5p, miR-6768-5p, miR-92b-5p, miR-3679-5p, miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513, miR-6781-5p, miR-4649-5pAt least one polynucleotide selected from the group consisting of miR-6775-5p, miR-4651, miR-3195, miR-6726-5p, miR-6872-3p, miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975, miR-6821-5p, miR-4534, miR-619-5p, miR-7107-5p, miR-1228-3p, miR-6774-5p, miR-6805-5p, miR-23a-3p, miR-4665-5p, miR-4505, miR-4638-5p, miR-24-3p, miR-3135b, miR-4745-5p, miR-128-1-5p, miR-4476, miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141, miR-3188, miR-4281, miR-5196-5p, miR-6880-5p, miR-3960, miR-3648, miR-6721-5p, miR-4492, miR-744-5p, miR-7704, miR-4749-5p, miR-6794-5p, miR-6824-5p, miR-762, miR-6836-3p, miR-6727-5p, miR-7977, miR-4484, miR-6515-3p, miR-373-5p, miR-4258, miR-4674, miR-3180, miR-6076, miR-1238-5p, miR-4463, miR-4486, and miR-4730, and a nucleic acid probe capable of specifically binding to the polynucleotide and / or a primer that specifically recognizes and amplifies the polynucleotide. The kit according to claim 1 or 2.
4. The nucleic acid probe and / or primer is a polynucleotide selected from the group consisting of the following polynucleotides (f) to (j): (f) A polynucleotide consisting of the nucleotide sequence represented by any of SEQ ID NOs: 1 to 13, 15 to 21, 23 to 54, 56 to 83, 84 to 226, 227 to 229, and 230 to 245 or a nucleotide sequence in which u is t in the nucleotide sequence, or a fragment thereof containing 19 or more consecutive bases, (g) A polynucleotide containing the nucleotide sequence represented by any of SEQ ID NOs: 1 to 13, 15 to 21, 23 to 54, 56 to 83, 84 to 226, 227 to 229, and 230 to 245, (h) A polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 13, 15 to 21, 23 to 54, 56 to 83, 84 to 226, 227 to 229, and 230 to 245 or a nucleotide sequence in which u is t in the nucleotide sequence, or a fragment thereof containing 19 or more consecutive bases, (i)a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 1 to 13, 15 to 21, 23 to 54, 56 to 83, 84 to 226, 227 to 229, and 230 to 245, or a base sequence complementary to a base sequence in which u is t in the base sequence, and (j)a polynucleotide that hybridizes with any one of the polynucleotides of (f) to (i) above under stringent conditions, The kit according to claim 3, which is a polynucleotide selected from the group consisting of.
5. A device for detecting early pancreatic cancer or pancreatic cancer precursor lesions, comprising a nucleic acid probe that can specifically bind to a polynucleotide of miR-4632-5p, which is a marker for early pancreatic cancer or pancreatic cancer precursor lesions, and / or a primer that specifically recognizes and amplifies the polynucleotide.
6. The nucleic acid probe and / or primer is a polynucleotide shown in any one of the following (a) to (e): (a)a polynucleotide consisting of the base sequence represented by SEQ ID NO: 55 or a base sequence in which u is t in the base sequence, or a fragment thereof containing 19 or more consecutive bases, (b)a polynucleotide containing the base sequence represented by SEQ ID NO: 55, (c)a polynucleotide consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 55 or a base sequence in which u is t in the base sequence, or a fragment thereof containing 19 or more consecutive bases, (d)a polynucleotide containing a base sequence complementary to the base sequence represented by SEQ ID NO: 55 or a base sequence in which u is t in the base sequence, and (e)a polynucleotide that hybridizes with any one of the polynucleotides of (a) to (d) above under stringent conditions, The device according to claim 5, which is a polynucleotide selected from the group consisting of.
7. The device is another early pancreatic cancer or pancreatic cancer precursor lesion marker, including miR-6784-5p, miR-1181, miR-671-5p, miR-6857-5p, miR-4276, miR-1914-3p, miR-149-3p, miR-937-5p, miR-4675, miR-6795-5p, miR-4731-5p, miR-5090, miR-3620-5p, miR-6717-5p, miR-6825-5p, miR-6738-5p, miR-6769a-5p, miR-4728-5p, miR-652-5p, miR-4257, miR-7110-5p, miR-6887-5p, miR-887-3p, miR-1228-5p, miR-5572, miR-6782-5p, miR-4298, miR-6786-5p, miR-5010-5p, miR-6087, miR-6765-5p, miR-6732-5p, miR-6787-5p, miR-6737-5p, miR-128-2-5p, miR-4270, miR-6861-5p, miR-6756-5p, miR-1229-5p, miR-6891-5p, miR-6848-5p, miR-1237-5p, miR-30c-1-3p, miR-1233-5p, miR-211-3p, miR-4758-5p, miR-614, miR-6746-5p, miR-1915-5p, miR-4688, miR-3917, miR-5787, miR-6126, miR-135a-3p, miR-8063, miR-5698, miR-6089, miR-498, miR-296-3p, miR-4419b, miR-6802-5p, miR-6829-5p, miR-6803-5p, miR-1199-5p, miR-6840-3p, miR-6752-5p, miR-6798-5p, miR-6131, miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920, miR-23b-3p, miR-4448, miR-2110, miR-4706, miR-7845-5p, miR-6808-5p, miR-4447, miR-6869-5p, miR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125, miR-3178, miR-3196, miR-8069,miR-4723-5p, miR-4746-3p, miR-4689, miR-6816-5p, miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p, miR-6875-5p, miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p, miR-4695-5p, miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p, miR-3185, miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p, miR-1343-3p, miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p, miR-5100, miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718, miR-6780b-5p, miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p, miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a, miR-6791-5p, miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449, miR-4707-3p, miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p, miR-204-3p, miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p, miR-675-5p, miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p, miR-3162-5p, miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p, miR-7113-3p, miR-6850-5p, miR-6799-5p, miR-6768-5p, miR-92b-5p, miR-3679-5p, miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513, miR-6781-5pAt least one polynucleotide selected from the group consisting of miR-4649-5p, miR-6775-5p, miR-4651, miR-3195, miR-6726-5p, miR-6872-3p, miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975, miR-6821-5p, miR-4534, miR-619-5p, miR-7107-5p, miR-1228-3p, miR-6774-5p, miR-6805-5p, miR-23a-3p, miR-4665-5p, miR-4505, miR-4638-5p, miR-24-3p, miR-3135b, miR-4745-5p, miR-128-1-5p, miR-4476, miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141, miR-3188, miR-4281, miR-5196-5p, miR-6880-5p, miR-3960, miR-3648, miR-6721-5p, miR-4492, miR-744-5p, miR-7704, miR-4749-5p, miR-6794-5p, miR-6824-5p, miR-762, miR-6836-3p, miR-6727-5p, miR-7977, miR-4484, miR-6515-3p, miR-373-5p, miR-4258, miR-4674, miR-3180, miR-6076, miR-1238-5p, miR-4463, miR-4486, and miR-4730, and a nucleic acid probe capable of specifically binding to the polynucleotide and / or a primer capable of specifically recognizing and amplifying the polynucleotide. The device according to claim 5 or 6.
8. The nucleic acid probe and / or primer is a polynucleotide shown in any one of the following (f) to (j): (f)a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 1 to 13, 15 to 21, 23 to 54, 56 to 83, 84 to 226, 227 to 229, and 230 to 245, or a base sequence in which u is t in the base sequence, or a fragment thereof containing 19 or more consecutive bases, (g) a polynucleotide containing the base sequence represented by any one of SEQ ID NOs: 1 to 13, 15 to 21, 23 to 54, 56 to 83, 84 to 226, 227 to 229, and 230 to 245, (h) A polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 13, 15 to 21, 23 to 54, 56 to 83, 84 to 226, 227 to 229, and 230 to 245 or a base sequence complementary to the base sequence in which u is t in the base sequence, or a fragment thereof containing 19 or more consecutive bases, (i) A polynucleotide containing a base sequence represented by any one of SEQ ID NOs: 1 to 13, 15 to 21, 23 to 54, 56 to 83, 84 to 226, 227 to 229, and 230 to 245 or a base sequence complementary to the base sequence in which u is t in the base sequence, and (j) A polynucleotide that hybridizes with any one of the polynucleotides of (f) to (i) under stringent conditions, The device according to claim 7, which is a polynucleotide selected from the group consisting of.
9. The device according to any one of claims 5 to 8, wherein the device is a device for measurement by a hybridization technique.
10. The device according to claim 9, wherein the hybridization technique is a nucleic acid array technique.
11. Measure the expression level of miR-4632-5p in a sample of a subject using the kit according to any one of claims 1 to 4 or the device according to any one of claims 5 to 10, and compare the measured expression level of the subject with the control expression level of a healthy subject measured in the same manner. When the expression level of the subject is higher than the control expression level of the healthy subject, it is evaluated in vitro that the subject is suffering from early pancreatic cancer or a pancreatic cancer precursor lesion. A method for assisting the detection of early pancreatic cancer or a pancreatic cancer precursor lesion in a subject.
12. Measure the expression level of miR-4632-5p in a sample of a subject using the kit according to any one of claims 1 to 4 or the device according to any one of claims 5 to 10, and use the gene expression levels of samples from subjects known to have early pancreatic cancer or pancreatic cancer precursor lesions and samples from healthy subjects as training samples. Substitute the expression level of miR-4632-5p in the sample from the subject into a discriminant formula that can distinguish between early pancreatic cancer or pancreatic cancer precursor lesions and health, thereby evaluating the presence or absence of early pancreatic cancer or pancreatic cancer precursor lesions. A method for assisting the detection of early pancreatic cancer or a pancreatic cancer precursor lesion in a subject.
13. The method according to claim 11 or 12, wherein the subject is a human.
14. The method according to any one of claims 11 to 13, wherein the sample is blood, serum or plasma.
15. Use of a polynucleotide of miR-4632-5p as an early pancreatic cancer or pancreatic cancer precursor lesion marker for detecting early pancreatic cancer or pancreatic cancer precursor lesions.
16. miR-6784-5p, miR-1181, miR-671-5p, miR-6857-5p, miR-4276, miR-1914-3p, miR-149-3p, miR-937-5p, miR-4675, miR-6795-5p, miR-4731-5p, miR-5090, miR-3620-5p, miR-6717-5p, miR-6825-5p, miR-6738-5p, miR-6769a-5p, miR-4728-5p, miR-652-5p, miR-4257, miR-7110-5p, miR-6887-5p, miR-887-3p, miR-1228-5p, miR-5572, miR-6782-5p, miR-4298, miR-6786-5p, miR-5010-5p, miR-6087, miR-6765-5p, miR-6732-5p, miR-6787-5p, miR-6737-5p, miR-128-2-5p, miR-4270, miR-6861-5p, miR-6756-5p, miR-1229-5p, miR-6891-5p, miR-6848-5p, miR-1237-5p, miR-30c-1-3p, miR-1233-5p, miR-211-3p, miR-4758-5p, miR-614, miR-6746-5p, miR-1915-5p, miR-4688, miR-3917, miR-5787, miR-6126, miR-135a-3p, miR-8063, miR-5698, miR-6089, miR-498, miR-296-3p, miR-4419b, miR-6802-5p, miR-6829-5p, miR-6803-5p, miR-1199-5p, miR-6840-3p, miR-6752-5p, miR-6798-5p, miR-6131, miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920, miR-23b-3p, miR-4448, miR-2110, miR-4706, miR-7845-5p, miR-6808-5p, miR-4447, miR-6869-5p, miR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125, miR-3178, miR-3196, miR-8069, miR-4723-5p, miR-4746-3p, miR-4689miR-6816-5p, miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p, miR-6875-5p, miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p, miR-4695-5p, miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p, miR-3185, miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p, miR-1343-3p, miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p, miR-5100, miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718, miR-6780b-5p, miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p, miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a, miR-6791-5p, miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449, miR-4707-3p, miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p, miR-204-3p, miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p, miR-675-5p, miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p, miR-3162-5p, miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p, miR-7113-3p, miR-6850-5p, miR-6799-5p, miR-6768-5p, miR-92b-5p, miR-3679-5p, miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513, miR-6781-5p, miR-4649-5p, miR-6775-5p, miR-4651, miR-3195The use according to claim 15, further comprising at least one polynucleotide selected from the group consisting of miR-6726-5p, miR-6872-3p, miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975, miR-6821-5p, miR-4534, miR-619-5p, miR-7107-5p, miR-1228-3p, miR-6774-5p, miR-6805-5p, miR-23a-3p, miR-4665-5p, miR-4505, miR-4638-5p, miR-24-3p, miR-3135b, miR-4745-5p, miR-128-1-5p, miR-4476, miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141, miR-3188, miR-4281, miR-5196-5p, miR-6880-5p, miR-3960, miR-3648, miR-6721-5p, miR-4492, miR-744-5p, miR-7704, miR-4749-5p, miR-6794-5p, miR-6824-5p, miR-762, miR-6836-3p, miR-6727-5p, miR-7977, miR-4484, miR-6515-3p, miR-373-5p, miR-4258, miR-4674, miR-3180, miR-6076, miR-1238-5p, miR-4463, miR-4486, and miR-4730, or a fragment thereof containing 19 or more consecutive bases.
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