A test kit or device for early pancreatic cancer or precancerous lesion of pancreatic cancer and a test method
Patent Information
- Application Number
- CN201780012295.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2016-03-31
- Filing Date
- 2017-03-31
- Publication Date
- 2026-10-09
- Estimated Expiration
- 2037-03-31
AI Technical Summary
然而,肿瘤标志物的评价大多是针对晚期胰癌的研究,在早期胰癌中大多不显示异常值
[0391] According to the present invention, early pancreatic cancer or precancerous lesions of pancreatic cancer can be detected easily and with high accuracy.
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Figure CN108699607B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a kit or device for detecting early pancreatic cancer or precancerous pancreatic lesions, comprising a nucleic acid capable of specifically binding to a specific miRNA, for examining whether a subject has early pancreatic cancer or precancerous pancreatic lesions, and a method for detecting early pancreatic cancer or precancerous pancreatic lesions comprising using the nucleic acid to determine the expression level of the miRNA. Background Technology
[0002] The pancreas is an exocrine gland that secretes pancreatic juice, which is a digestive fluid, and is sent 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 bloodstream.
[0003] Because the pancreas is surrounded by multiple organs such as the stomach, duodenum, small intestine, liver, and gallbladder, early detection of pancreatic cancer is difficult. Furthermore, pancreatic cancer is characterized by its lack of noticeable symptoms, rapid progression, and tendency to metastasize to other organs, resulting in an extremely poor prognosis compared to other cancers. According to statistics on cancer mortality rates by site in Japan in 2011 published by the Cancer Countermeasures Information Center of the National Cancer Center (Tokyo, Japan), the number of deaths from pancreatic cancer rose to 28,829. The 5-year relative survival rate by site between 2003 and 2005 was lowest for pancreatic cancer, at 7.1% for men and 6.9% for women.
[0004] As described in Non-Patent Literature 1, pancreatic cancer treatment is generally administered based on progression through surgery, systemic chemotherapy, radiotherapy, or a combination thereof. In order to achieve a cure, 15–20% of pancreatic cancer patients undergo surgery, but it is believed that most patients who do not undergo surgery have either local progression or metastasis.
[0005] The UICC (Unio Internationalis Contra Cancrum) classifies pancreatic cancer progression into stages 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 diagnosis is more than 70% in stages IVa and IVb. As described in Non-Patent Literature 1, the 5-year survival rate for 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. The prognosis for stages III and IV is extremely poor, therefore early detection and treatment of pancreatic cancer are crucial.
[0006] As described in Non-Patent Literature 2, abdominal ultrasound is a simple and low-invasive examination that is very useful in outpatient clinics and examinations for the diagnosis of pancreatic cancer. However, it is difficult to depict pancreatic cancers with small tumor diameters and lesions in the caudal region of the pancreas. The abnormality detection rate of pancreatic images obtained by abdominal ultrasound in routine health checkups is about 1%, and the pancreatic cancer detection rate is as low as about 0.06% or less. In addition, tumor markers used for pancreatic cancer detection include, for example, known glycan antigens such as CA19-9, Span-1, CA50, CA242, Dupan-2, TAG-72, and urinary fucose, and known non-glycan antigens such as CEA, POA, and TPS. As a method of using these tumor markers, cancer is suspected when their blood concentration is higher or lower than a pre-set baseline value. For example, as described in Non-Patent Literature 3, the baseline value for CEA is set at 5 ng / mL, and the baseline value for CA19-9 is set at 37 U / mL. Cancer including pancreatic cancer is suspected when values above these are displayed. However, the evaluation of tumor markers is mostly based on studies of advanced pancreatic cancer, and they generally do not show abnormal values in early-stage pancreatic cancer. Furthermore, even when tumor markers and abdominal ultrasound are performed during examination, the detection rate of pancreatic cancer is low, making the implementation of these diagnostic methods for pancreatic cancer cost-effective.
[0007] On the other hand, cystic diseases occurring in the pancreas are known to develop into invasive carcinomas and can be considered precancerous lesions of pancreatic cancer. As described in Non-Patent Literature 4, the malignancy of cystic diseases is evaluated based on factors such as cyst diameter, wall thickening, main pancreatic duct diameter, wall nodules, main pancreatic duct stenosis, lymph node enlargement, and cystic lesions. In the case of intraductal papillary mucinous tumors, which are a type of cystic disease, the prognosis is poor, with a malignancy rate of 40.4% and an invasive carcinoma rate of 30.8%. Therefore, even if the malignancy is low at the time of discovery, observation and resection are recommended.
[0008] Although it is in the research stage, as shown in Patent Documents 1-5 and Non-Patent Document 4, there are reports of pancreatic cancer being identified by measuring the expression level of microRNAs (miRNAs) in biological samples, such as blood, or by combining the expression levels of miRNAs with those of other protein markers.
[0009] Patent document 1 describes 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, and hsa-miR-5195-3p in the blood.
[0011] Patent document 3 shows a method for detecting pancreatic cancer by combining miR-23a-3p in the blood with dozens of other miRNAs.
[0012] Patent document 4 lists hsa-miR-1268a, hsa-miR-939-5p, and hsa-miR-642b-3p as miRNAs that are expressed at higher levels in the blood of pancreatic cancer patients than in healthy individuals, and demonstrates methods for detecting pancreatic cancer and evaluating the risk of developing pancreatic cancer by combining them with dozens of other miRNAs.
[0013] Patent document 5 shows a method for detecting pancreatic cancer, precancerous lesions of pancreatic cancer, and evaluating the risk of developing pancreatic cancer by combining hsa-miR-296-5p in the blood with dozens of other miRNAs.
[0014] Non-patent literature 5 lists hsa-miR-638, hsa-miR-3196, and hsa-miR-1225-3p as miRNAs that are expressed at higher levels in the blood of pancreatic cancer patients than in healthy individuals, and demonstrates a method for detecting pancreatic cancer by combining several of these miRNAs.
[0015] Existing technical documents
[0016] Patent documents
[0017] Patent Document 1: Japanese Patent Application Publication No. 2015-107091
[0018] Patent Document 2: International Publication No. 2015 / 182781
[0019] Patent Document 3: U.S. Patent Application Publication No. 2015 / 0011414
[0020] Patent Document 4: Japanese Patent Publication No. 2015-502176
[0021] Patent Document 5: International Publication No. 2015 / 153679
[0022] Non-patent literature
[0023] Non-patent literature 1: Tetsuya Mine, "Pancreas", Japanese Society of Pancreatology, 2007, Vol.22, pp.10-13
[0024] Non-Patent Literature 2: Japanese Pancreatic Society's "Scientifically Based Pancreatic Cancer Diagnosis and Treatment Guidelines (2009 Edition)" CQ1 Diagnostic Method http: / / www.suizou.org / PCMG2009 / cq1 / cq1-3.html
[0025] Non-patent literature 3: Kiyoshi Kurokawa et al., eds., Clinical Examination Data Book, 2013, pp. 633, 636 (Medical Academy, Tokyo, Japan).
[0026] Non-patent literature 4: International Pancreatic Society Working Group, IPMN / MCN International Treatment Guidelines (2012 Edition), pp. 6, 8
[0027] Non-patent literature 5: Miyamae M et al., 2015, British Journal of Cancer, Vol. 113, (10) pp. 1467-1476 Summary of the Invention
[0028] The problem that the invention aims to solve
[0029] The objective of this invention is to find novel tumor markers for early pancreatic cancer or precancerous lesions of pancreatic cancer, and to provide a method for effectively detecting early pancreatic cancer or precancerous lesions of pancreatic cancer using nucleic acids that can specifically bind to these markers. As described in Non-Patent Literature 2, tumor markers used for pancreatic cancer detection include, for example, known glycan antigens such as CA19-9, Span-1, CA50, CA242, Dupan-2, TAG-72, and urinary fucose, or known antigens other than glycans such as CEA, POA, and TPS. Regarding the pancreatic cancer detection sensitivity of these tumor markers, CA19-9 is 70–80%, Span-1 is 70–80%, Dupan-2 is 50–60%, CEA is 30–60%, and CA50 is 60%. Furthermore, their specificity is not very high, and false positives are as high as 20–30%. Therefore, it is also considered that there is a possibility of misdiagnosing other cancers and / or benign tumors and / or benign diseases of the pancreas and / or surrounding organs. Furthermore, the detection sensitivity for early-stage pancreatic cancer is typically low. For pancreatic cancer smaller than 2 cm, the positive rate for CA19-9 is only 52%, which is less than half, making it useless for detecting early-stage pancreatic cancer. Additionally, tumor markers using sugar chain antigens do not produce antigens in Lewis blood type negative cases, resulting in false negatives, making them unsuitable for some patients. Moreover, the detection rates of MRI and CT for intraductal papillary mucinous tumors, which are precancerous lesions of pancreatic cancer, are only 19.9% and 1.2–2.6%, respectively, which is insufficient, and the use of tumor markers is not recommended for detecting precancerous lesions of pancreatic cancer.
[0030] Furthermore, although it is still in the research stage, there are reports such as using the expression level of microRNA (miRNA) in biological samples, represented by blood, to identify pancreatic cancer, but none of these methods have been put into practical use as a detection method for early pancreatic cancer or precancerous lesions of pancreatic cancer.
[0031] Patent document 1 describes a method for detecting pancreatic cancer by combining miR-125a-3p, miR-204-3p, miR-3648 in the blood with several other miRNAs. However, only healthy individuals were used as the negative control group for pancreatic cancer. There is no record of cancer or benign diseases of organs other than the pancreas, nor is there a record of using blood to detect specific precancerous lesions of pancreatic cancer.
[0032] Patent document 2 shows a method for detecting pancreatic cancer by combining miRNAs such as hsa-miR-1908-5p, hsa-miR-6729-5p, and hsa-miR-5195-3p in the blood. However, it only includes a few samples of early pancreatic cancer patients and does not describe the specific accuracy, sensitivity, or specificity of the detection performance for early pancreatic cancer, nor does it describe a method for detecting specific precancerous lesions of pancreatic cancer using blood.
[0033] Patent document 3 describes a method for detecting pancreatic cancer by combining hsa-miR-23a-3p in the blood with dozens of other miRNAs, but it does not describe the specific accuracy, sensitivity, specificity, or other performance characteristics of the detection for early pancreatic cancer. As a negative control group for pancreatic cancer, it does not describe any cancers other than those in the upper gastrointestinal tract surrounding the pancreas, nor does it describe a method for detecting precancerous lesions of pancreatic cancer.
[0034] Patent document 4 shows a method for detecting pancreatic cancer and precancerous lesions of pancreatic cancer by combining hsa-miR-1268a, hsa-miR-939-5p, and hsa-miR-642b-3p with dozens of other miRNAs, but there is no record of the specific accuracy, sensitivity, specificity, or other detection performance for pancreatic cancer. As a negative control group for pancreatic cancer, there is also no record of cancers of organs other than the pancreas.
[0035] Patent document 5 shows a method for detecting pancreatic cancer and precancerous lesions of pancreatic cancer by combining hsa-miR-296-5p in blood with dozens of other miRNAs, but it does not record the specific accuracy, sensitivity, specificity and other detection performance of early pancreatic cancer. As a negative control group for precancerous lesions of pancreatic cancer, it does not measure cancer or benign diseases of organs other than the pancreas, and it does not record the specificity.
[0036] Non-patent literature 5 lists hsa-miR-638, hsa-miR-3196, and hsa-miR-1225-3p as miRNAs whose expression levels are increased in the blood of pancreatic cancer patients compared to healthy individuals. It shows a method for detecting pancreatic cancer by combining several of these miRNAs. However, as a negative control group for pancreatic cancer, there is no record of cancers in organs other than the pancreas.
[0037] Thus, in the detection of early pancreatic cancer or precancerous lesions, existing tumor markers have low performance, or lack specific performance and detection methods for markers in the research stage. Therefore, their use may lead to misdiagnosis of healthy individuals as early pancreatic cancer or precancerous lesions, resulting in unnecessary additional testing, or missed detection of early pancreatic cancer or precancerous lesions, leading to lost treatment opportunities. Furthermore, measuring dozens to hundreds of miRNAs increases testing costs, making it unsuitable for large-scale screening in health diagnostics. Additionally, collecting pancreatic tissue for tumor marker measurement is highly invasive and not preferred. Therefore, there is a need for early pancreatic cancer or precancerous lesion markers that can be detected in blood with low invasiveness, accurately distinguishing between early pancreatic cancer or precancerous lesions and healthy individuals. In particular, early detection and resection of pancreatic cancer is the only radical treatment; therefore, highly sensitive early pancreatic cancer or precancerous lesion markers are urgently needed.
[0038] Methods for solving problems
[0039] In order to solve the above-mentioned problems, the inventors conducted in-depth research and found several genes in blood that can be collected in a low-invasive manner as biomarkers for the detection of early pancreatic cancer or precancerous lesions of pancreatic cancer. They also discovered that by using nucleic acids that can specifically bind to these genes, it is possible to meaningfully detect early pancreatic cancer or precancerous lesions of pancreatic cancer, thus completing the present invention.
[0040] <Summary of the Invention>
[0041] That is, the present invention has the following features.
[0042] (1) A kit for detecting early pancreatic cancer or precancerous lesions of pancreatic cancer, comprising nucleic acids capable of specifically binding to biomarkers of early pancreatic cancer or precancerous lesions of pancreatic cancer, wherein the biomarkers are selected from 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, and m iR-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,m iR-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-6 14.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,mi R-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,At least one polynucleotide from the group consisting of miR-6511a-5p, miR-6824-5p, miR-6766-3p, miR-6511a-5p, and miR-6749-5p.
[0043] (2) According to the kit described in (1), wherein 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-47 28-5p 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-6 126, 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-6 803-5p, 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, and 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.
[0044] (3) According to the kit described in (1) or (2), the above-mentioned nucleic acid is a polynucleotide selected from the group consisting of polynucleotides shown in any one of (a) to (e) below.
[0045] (a) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 1–83, 227–229, 246, 248, and 250, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.
[0046] (b) A polynucleotide containing the base sequence shown in any of the sequence numbers 1–83, 227–229, 246, 248, and 250.
[0047] (c) A polynucleotide, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, consisting of a base sequence complementary to the base sequence represented by any of the sequence numbers 1–83, 227–229, 246, 248, and 250, or a base sequence in which u is t.
[0048] (d) A polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequence numbers 1–83, 227–229, 246, 248, and 250, or a base sequence in which u is t, and
[0049] (e) A polynucleotide that hybridizes with any of the polynucleotides (a) to (d) above under strict conditions.
[0050] (4) The kit according to any one of (1) to (3), wherein the kit further comprises a nucleic acid capable of specifically binding to other early pancreatic cancer or precancerous pancreatic cancer markers, said other early pancreatic cancer or precancerous pancreatic cancer markers being selected from 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-12 25-3p,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-764 1.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-44 88.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,mi R-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-44 17.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-36 22a-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-3195, miR-67 26-5p, 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, m iR-4749-5p, miR-762, miR-6836-3p, miR-6727-5p, miR-4739, miR-7977, miR-4484, miR-6515-3p, miR-373-5p, miR-425 8、miR-4674、miR-3180、miR-6076、miR-1238-5p、miR-4463、 miR-4486、miR-4730、miR-4286 and miR-4739。、
[0051] (5) The kit according to (4), wherein 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, and miR-4746-3 p 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, and 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 The following are listed: hsa-miR-6845-5p, miR-4741, miR-4467, miR-4707-5p, miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a, and miR-6791-5p. iR-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, and 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-mi R-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 The values are: hsa-miR-4476, miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141, miR-3188, miR-4281, miR-5196-5p, and miR-6880-5p. R-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-mi R-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, and miR-4739 is hsa-miR-4739.
[0052] (6) According to the kit described in (4) or (5), the above nucleic acid is a polynucleotide selected from the group consisting of polynucleotides shown in any one of (f) to (j) below.
[0053] (f) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 84–226, 230–245, 247, and 249, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.
[0054] (g) A polynucleotide containing the base sequence shown in any of the sequence numbers 84–226, 230–245, 247, and 249.
[0055] (h) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 84–226, 230–245, 247, and 249, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.
[0056] (i) a polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequences 84–226, 230–245, 247, and 249, or a base sequence in which u is t, and
[0057] (j) A polynucleotide that hybridizes with any of the polynucleotides (f) to (i) above under strict conditions.
[0058] (7) A device for detecting early pancreatic cancer or precancerous lesions of pancreatic cancer, comprising a nucleic acid capable of specifically binding to a biomarker for early pancreatic cancer or precancerous lesions of pancreatic cancer, wherein the biomarker for early pancreatic cancer or precancerous lesions of pancreatic cancer is selected from 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-6784-5p, miR-1181, miR-6717-5p, miR-6825-5p, miR-6784-5p, miR-1181, miR-671-5p, miR-6795-5p, miR-6731-5p, miR-5090, miR-3620-5p, miR-1343-5p, miR-6717-5p, miR-6825-5p, miR-6784-5p, miR-1181 ...784-5p, miR-1181, miR-6717-5p, miR-6784-5p, miR-1181, R-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,m iR-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,mi R-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-61 4.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,mi R-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,At least one polynucleotide from miR-6511a-5p, miR-6824-5p, miR-6766-3p, miR-6511a-5p, and miR-6749-5p.
[0059] (8) The device according to (7), wherein 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-47 28-5p 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-6 126, 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-6 803-5p, 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, and 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.
[0060] (9) According to the device described in (7) or (8), the nucleic acid is a polynucleotide selected from the group consisting of polynucleotides shown in any one of (a) to (e) below.
[0061] (a) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 1–83, 227–229, 246, 248, and 250, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.
[0062] (b) A polynucleotide containing the base sequence shown in any of the sequence numbers 1–83, 227–229, 246, 248, and 250.
[0063] (c) A polynucleotide, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, consisting of a base sequence complementary to the base sequence represented by any of the sequence numbers 1–83, 227–229, 246, 248, and 250, or a base sequence in which u is t.
[0064] (d) A polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequence numbers 1–83, 227–229, 246, 248, and 250, or a base sequence in which u is t, and
[0065] (e) A polynucleotide that hybridizes with any of the polynucleotides (a) to (d) above under strict conditions.
[0066] (10) The device according to any one of (7) to (9), wherein the device further comprises a nucleic acid capable of specifically binding to another early pancreatic cancer or precancerous lesion marker, said other early pancreatic cancer or precancerous lesion marker being selected from 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-122 5-3p,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-448 8.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,mi R-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-44 17.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-36 22a-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-3195, miR-67 26-5p, 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, m iR-4749-5p, miR-762, miR-6836-3p, miR-6727-5p, miR-4739, miR-7977, miR-4484, miR-6515-3p, miR-373-5p, miR-425 8、miR-4674、miR-3180、miR-6076、miR-1238-5p、miR-4463、 miR-4486、miR-4730、miR-4286 and miR-4739。、
[0067] (11) The device according to (10), wherein 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 hs a-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, and 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 The following are listed: hsa-miR-6845-5p, miR-4741, miR-4467, miR-4707-5p, miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a, and miR-6791-5p. iR-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, and 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-mi R-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 The values are: hsa-miR-4476, miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141, miR-3188, miR-4281, miR-5196-5p, and miR-6880-5p. R-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-mi R-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, and miR-4739 is hsa-miR-4739.
[0068] (12) According to the device described in (10) or (11), the nucleic acid is a polynucleotide selected from the group consisting of polynucleotides shown in any one of (f) to (j) below.
[0069] (f) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 84–226, 230–245, 247, and 249, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.
[0070] (g) A polynucleotide containing the base sequence shown in any of the sequence numbers 84–226, 230–245, 247, and 249.
[0071] (h) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 84–226, 230–245, 247, and 249, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.
[0072] (i) a polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequences 84–226, 230–245, 247, and 249, or a base sequence in which u is t, and
[0073] (j) A polynucleotide that hybridizes with any of the polynucleotides (f) to (i) above under strict conditions.
[0074] (13) The device according to any one of (7) to (12) is a device for determination by hybridization technique.
[0075] (14) According to the device described in (13), the above hybridization technique is a nucleic acid array technique.
[0076] (15) A method for detecting early pancreatic cancer or precancerous lesions of pancreatic cancer in a subject, comprising: using a kit described in any one of (1) to (6) or a device described in any one of (7) to (14) to determine the expression level of a target nucleic acid in a sample of the subject, using the determined expression level and a control expression level of a healthy body also determined in vitro to evaluate whether the subject has early pancreatic cancer or precancerous lesions of pancreatic cancer, or does not have early pancreatic cancer or precancerous lesions of pancreatic cancer, thereby detecting whether early pancreatic cancer or precancerous lesions of pancreatic cancer are present or absent in the subject.
[0077] (16) A method for detecting early pancreatic cancer or precancerous lesions of pancreatic cancer in a subject, comprising: measuring the expression level of a target gene in a sample of the subject using a kit described in any one of (1) to (6) or a device described in any one of (7) to (14), and substituting the expression level of the target gene from the sample of the subject into a discriminant expression (discriminant function) to evaluate whether early pancreatic cancer or precancerous lesions of pancreatic cancer are present or absent.
[0078] The discriminant (discriminant function) is prepared by using the gene expression levels of samples from subjects known to have early pancreatic cancer or precancerous lesions and the gene expression levels of samples from healthy subjects as teacher samples, and is able to distinguish between early pancreatic cancer or precancerous lesions and healthy subjects.
[0079] (17) The subject described above is a human being, as described in (15) or (16).
[0080] (18) The sample described in any one of (15) to (17) is blood, serum or plasma.
[0081] <Definition of Terms>
[0082] The terms used in this specification have the following definitions.
[0083] In this manual, "pancreatic cancer" refers to invasive ductal carcinomas. Specifically, it includes papillary adenocarcinoma, tubular adenocarcinoma, poorly differentiated adenocarcinoma, adenosquamous carcinoma, mucinous carcinoma, and anaplastic carcinoma, all of which form within the pancreas ("Pancreatic Cancer Treatment Guidelines," 6th revised edition, 2013, Japanese Pancreatic Society, Kinbara Publishing (Tokyo, Japan), pp. 27-28).
[0084] In this instruction manual, "precancerous lesions of the pancreas" refers to exocrine neoplasms that form within the pancreas. Specifically, this includes serous cystic neoplasms (SCNs), serous cystadenoma (SCA), serous cystadenocarcinoma (SCC), mucinous cystic neoplasms (MCNs), mucinous cystadenoma (MCA), mucinous cystadenocarcinoma (MCC), and intraductal mammary glands. 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 Society of Pancreatology, Kinbara Publishing (Tokyo, Japan), pp. 24-27).
[0085] In this manual, the "progression of pancreatic cancer" is classified into stages 0, IA, IB, IIA, IIB, III, IVa, and IVb based on the local progression of the main tumor, lymph node metastasis, and distant metastasis ("Pancreatic Cancer Treatment Guidelines", 6th revised edition, 2013, Japanese Society of Pancreatology, Kinbara Publishing (Tokyo, Japan), pp. 55-57).
[0086] In this instruction manual, "early stage pancreatic cancer" refers to pancreatic cancer in stages 0, IA, IB, IIA, and IIB.
[0087] In this instruction manual, "advanced pancreatic cancer" refers to stage III, IVa, and IVb pancreatic cancer.
[0088] In this instruction manual, "benign disease" refers to a non-malignant tumor involving an organ.
[0089] Furthermore, the abbreviations used in this specification, such as "nucleotide," "polynucleotide," "DNA," and "RNA," are in accordance with the "Guidelines for the Production of Instructions, etc., Containing Base Sequences or Amino Acid Sequences" (edited by the Japanese Patent Office) and the conventional meanings in this technical field.
[0090] In this specification, the term "polynucleotide" refers to nucleic acids comprising any of RNA, DNA, and RNA / DNA (chimeras). Furthermore, the aforementioned DNA includes any of cDNA, genomic DNA, and synthetic DNA. Additionally, the aforementioned 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 using, for example, an automated nucleic acid synthesizer, based on a specified base sequence (which can be either a native or non-native sequence). In this specification, "non-native sequence" is used in a broad sense to include sequences that differ from native sequences, such as sequences containing one or more substitutions, deletions, insertions, and / or additions (i.e., mutant sequences), sequences containing one or more modified nucleotides (i.e., modified sequences), etc. Furthermore, in this specification, "polynucleotide" and "nucleic acid" are used interchangeably.
[0091] In this specification, a “fragment” is a polynucleotide having a continuous portion of a polynucleotide sequence, preferably having a length of 15 or more bases, more preferably 17 or more bases, and more preferably 19 or more bases.
[0092] In this specification, the term "gene" is used to refer not only to RNA and double-stranded DNA, but also to the single-stranded DNA, including the positive (or sense) strand or complementary (or antisense) strand that constitutes them. Furthermore, there is no particular limitation on its length.
[0093] Therefore, unless otherwise specified, the term "gene" in this specification includes: double-stranded DNA containing human genomic DNA, single-stranded DNA (positive strand), single-stranded DNA (complementary strand) having a sequence complementary to the positive strand (e.g., cDNA), microRNA (miRNA), fragments thereof, and their transcripts. Furthermore, the term "gene" includes not only "genes" represented by a specific base sequence (or sequence number), but also "nucleic acids" encoding RNA with biological functions equivalent to the RNA encoded by that gene, such as those encoding homologs (i.e., orthologs), gene polymorphisms, mutants, and derivatives. Specifically, examples of such "nucleic acids" encoding homologs, mutants, or derivatives include those having a base sequence that hybridizes under the strict conditions described below with a complementary sequence of the base sequence shown in any of the sequence numbers 1 to 812 or a base sequence in which u is t. Additionally, regardless of the functional region, the term "gene" may include, for example, expression control regions, coding regions, exons, or introns. Furthermore, "genes" can be contained within cells, released outside cells and existing independently, or enclosed in vesicles called exogenous bodies.
[0094] In this specification, "exosome" refers to a small vesicle surrounded by a lipid bilayer secreted by cells. Exosomes originate from multivesicular endosomes and, when released into the extracellular environment, sometimes contain biological substances such as RNA, DNA (genes), and proteins. Exosomes are known to be found in bodily fluids such as blood, serum, plasma, and lymph.
[0095] In this specification, "transcription product" refers to RNA synthesized using a gene's DNA sequence as a template. RNA polymerase binds to a site upstream of the gene called the promoter, synthesizing RNA by binding ribonucleotides to the 3' end in a manner complementary to the DNA's base sequence. This RNA contains not only the gene itself but also the complete sequence from the transcription start site to the end of the poly-A sequence, represented by expression control regions, coding regions, exons, or introns.
[0096] Furthermore, unless otherwise specified, "microRNA (miRNA)" in this specification refers to a 15-25 base non-coding RNA that is transcribed as a hairpin-like RNA precursor, cleaved by a dsRNA cleaving enzyme with RNase III activity, encapsulated in a protein complex called RISC, and involved in the repression of mRNA translation. In addition, the term "miRNA" as used in this specification includes not only the "miRNA" indicated by a specific base sequence (or sequence number), but also its precursors (pre-miRNA, pri-miRNA), miRNAs with equivalent biological functions such as homologs (i.e., homologs or orthologs), mutants such as gene polymorphisms, and derivatives. Specifically, examples of such precursors, homologs, mutants, or derivatives include "miRNAs" that can be identified by miRBase version 20 (http: / / www.mirbase.org / ) and have a base sequence that hybridizes to the complementary sequence of any specific base sequence indicated by any of the sequence numbers 1-812 under the stringent conditions described below. In addition, the term “miRNA” used in this specification may refer to the gene product of a miR gene, which contains mature miRNA (e.g., a 15-25 base or 19-25 base non-coding RNA involved in the translation repression of mRNA as described above) or miRNA precursor (e.g., pre-miRNA or pri-miRNA as described above).
[0097] In this specification, a "probe" comprises a polynucleotide and / or a complementary polynucleotide used to specifically detect RNA or polynucleotides derived from gene expression.
[0098] In this specification, "primers" contain polynucleotides and / or complementary polynucleotides that specifically recognize and amplify RNA produced through gene expression or polynucleotides derived from such RNA.
[0099] Here, complementary polynucleotides (complementary strands, negative strands) refer to the full-length sequence or a portion thereof (here referred to as the positive strand for convenience) of a polynucleotide composed of a base sequence defined by any of the sequences 1 to 499, or a base sequence in that sequence where u is t, and which is complementary to the base pairing of A:T(U) and G:C. Furthermore, the description of a polynucleotide as "a complementary base sequence to the base sequence shown by any of the sequences 1 to 812, or a base sequence in that sequence where u is t" can be understood in essentially the same way.
[0100] In this specification, "stringent conditions" refer to conditions under which the nucleic acid probe hybridizes to its target sequence to a greater extent than it can detect other sequences (e.g., a value greater than the average of background measurements plus the standard error of the background measurements × 2). Stringent conditions are sequence-dependent and vary depending on the environment in which hybridization takes place. By controlling the stringency of hybridization and / or washing conditions, target sequences that are 100% complementary to the nucleic acid probe can be identified. Specific examples of "stringent conditions" are described later.
[0101] In this specification, "Tm value" refers to the temperature at which the double-stranded portion of a polynucleotide denatures into a single strand, with the double strand and single strand existing in a 1:1 ratio.
[0102] In this specification, "mutant" in the case of nucleic acids refers to a naturally occurring mutant caused by polymorphism, mutation, etc., or a mutant containing one or more (e.g., one to several) base deletions, substitutions, additions, or insertions in any base sequence of sequence numbers 1 to 812, or in a base sequence where u is t, or in a portion thereof, or a mutant showing approximately 90%, 95%, 97%, 98%, or 99% or more % identity with each of the base sequences or a portion thereof, or a nucleic acid that hybridizes with a polynucleotide or oligonucleotide containing the base sequence or a portion thereof under the strict conditions defined above.
[0103] In this specification, "several" refers to an integer of approximately 10, 9, 8, 7, 6, 5, 4, 3, or 2.
[0104] In this specification, mutants can be created using known techniques such as site-directed mutagenesis and mutation introduction using PCR.
[0105] In this specification, "% identity" can be determined using the protein or gene search systems described above, with or without gaps (Zheng Zhang et al., 2000, J. Comput. Biol., Vol. 7, pp. 203-214; Altschul, SF et al., 1990, Journal of Molecular Biology, Vol. 215, pp. 403-410; Pearson, WR et al., 1988, Proc. Natl. Acad. Sci. USA, Vol. 85, pp. 2444-2448).
[0106] In this specification, "derivative" refers to modified nucleic acids, and includes, without limitation, for example, labeled derivatives using fluorophores, derivatives containing modified nucleotides (e.g., nucleotides containing halogen, alkyl such as methyl, alkoxy such as methoxy, thio, carboxymethyl, etc., and nucleotides subjected to base reconstruction, double bond saturation, deamination, substitution of oxygen molecules for sulfur molecules, etc.), PNA (peptide nucleic acid; Nielsen, PE et al., 1991, Science, Vol. 254, pp. 1497-500), LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, pp. 5401-5404), etc.
[0107] In this specification, the "nucleic acid" that can specifically bind to the polynucleotides selected from the miRNAs mentioned above as markers of early pancreatic cancer or precancerous lesions is a synthetic or prepared nucleic acid. Specifically, it includes a "nucleic acid probe" or "primer" and is used directly or indirectly to detect the presence of early pancreatic cancer or precancerous lesions in a subject, or to diagnose the presence or severity of early pancreatic cancer or precancerous lesions, the degree of improvement, the sensitivity to treatment for early pancreatic cancer or precancerous lesions, or to screen for candidate substances useful for the prevention, improvement, or treatment of early pancreatic cancer or precancerous lesions. These include nucleotides, oligonucleotides, and polynucleotides that can specifically recognize and bind to the transcripts or cDNA of any of the sequences 1 to 812 in vivo, particularly in samples of bodily fluids such as blood and urine, in relation to the occurrence of early pancreatic cancer or precancerous lesions, to synthesize nucleic acids. Based on the aforementioned properties, these nucleotides, oligonucleotides, and polynucleotides can be effectively used as probes for detecting the expression of the aforementioned genes in organisms, tissues, and cells. In addition, they can be effectively used as primers for amplifying the expression of the aforementioned genes in organisms.
[0108] The term "test" as used in this specification may be replaced by terms such as examination, measurement, judgment, or judgment support. Furthermore, the term "evaluation" as used in this specification is used to imply support for diagnosis or evaluation based on examination or measurement results.
[0109] The term "subject" as used in this specification refers to mammals including humans, primates (such as chimpanzees), pet animals such as dogs and cats, livestock such as cattle, horses, sheep, and goats, rodents such as mice and rats, and animals kept in zoos. Humans are the preferred subject. Similarly, "healthy subjects" also refer to mammals that do not have the cancer being tested for. Humans are the preferred healthy subjects.
[0110] As used in this specification, "P" or "P-value" represents the probability, under the null hypothesis, of actually observing a statistic that is extreme compared to the statistic calculated from the data. Therefore, the smaller the "P" or "P-value," the more significant the difference is considered between the compared data.
[0111] In this instruction manual, "sensitivity" refers to the value of (number of true positives) / (number of true positives + number of false negatives). High sensitivity enables early detection of early pancreatic cancer or precancerous lesions, leading to complete resection of the cancerous portion and a reduced recurrence rate.
[0112] In this instruction manual, "specificity" refers to (number of true negatives) / (number of true negatives + number of false positives). High specificity can prevent unnecessary additional testing caused by misdiagnosing healthy individuals as having early pancreatic cancer or precancerous pancreatic lesions, thereby reducing the burden on patients and lowering medical costs.
[0113] In this instruction manual, "accuracy" refers to the value of (number of true positives + number of true negatives) / (total number of cases). Accuracy represents the proportion of correct judgments for all samples and serves as the primary indicator for evaluating test performance.
[0114] In this specification, the "sample" used as the object of judgment, detection, or diagnosis refers to tissue and biological materials in which the gene expression of the present invention changes with the occurrence, progression, or therapeutic effect of early pancreatic cancer or precancerous lesions. Specifically, this refers to pancreatic tissue and its surrounding blood vessels, lymph nodes, and organs, as well as organs suspected of metastasis, skin, and bodily fluids such as blood, urine, saliva, sweat, and tissue extracts, serum and plasma prepared from blood, as well as feces and hair. Further, it refers to biological samples extracted from these, specifically genes such as RNA and miRNA.
[0115] The terms "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" as used in this specification include the hsa-miR-6784-5p gene described in sequence number 1 (miRBase Accession No. MIMAT0027468), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6784-5p" is known as a precursor of "hsa-mir-6784" (miRBase Accession No. MI0022629, sequence number 251), which takes a hairpin-like structure.
[0116] As used in this specification, the terms "hsa-miR-1181 gene" or "hsa-miR-1181" include the hsa-miR-1181 gene described in sequence number 2 (miRBase Accession No. MIMAT0005826), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Subramanian S et al., 2008, Oncogene, Vol. 27, pp. 2015-2026. Additionally, "hsa-miR-1181" is known as a hairpin-like precursor, "hsa-mir-1181" (miRBase Accession No. MI0006274, sequence number 252).
[0117] The terms "hsa-miR-671-5p gene" or "hsa-miR-671-5p" as used in this specification include the hsa-miR-671-5p gene described in sequence number 3 (miRBase Accession No. MIMAT0003880), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Additionally, "hsa-miR-671-5p" is known as a hairpin-like precursor, "hsa-mir-671" (miRBase Accession No. MI0003760, sequence number 253).
[0118] The terms "hsa-miR-6857-5p gene" or "hsa-miR-6857-5p" as used in this specification include the hsa-miR-6857-5p gene described in sequence number 4 (miRBase Accession No. MIMAT0027614), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6857-5p" is known as a precursor of "hsa-mir-6857" (miRBase Accession No. MI0022703, sequence number 254), which takes a hairpin-like structure.
[0119] As used in this specification, the terms "hsa-miR-4276 gene" or "hsa-miR-4276" include the hsa-miR-4276 gene described in sequence number 5 (miRBase Accession No. MIMAT0016904), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Additionally, "hsa-miR-4276" is known as a hairpin-like precursor, "hsa-mir-4276" (miRBase Accession No. MI0015882, sequence number 255).
[0120] The terms "hsa-miR-1914-3p gene" or "hsa-miR-1914-3p" as used in this specification include the hsa-miR-1914-3p gene described in sequence number 6 (miRBase Accession No. MIMAT0007890), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Additionally, "hsa-miR-1914-3p" is known as a precursor of "hsa-mir-1914" (miRBase Accession No. MI0008335, sequence number 256), which takes a hairpin-like structure.
[0121] The terms "hsa-miR-149-3p gene" or "hsa-miR-149-3p" as used in this specification include the hsa-miR-149-3p gene described in sequence number 7 (miRBase Accession No. MIMAT0004609), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Lagos-Quintana M et al., 2002, CurrBiol, Vol. 12, pp. 735-739. Additionally, "hsa-miR-149-3p" is known as a precursor of "hsa-mir-149" (miRBase Accession No. MI0000478, sequence number 257), which takes a hairpin-like structure.
[0122] The terms "hsa-miR-937-5p gene" or "hsa-miR-937-5p" as used in this specification include the hsa-miR-937-5p gene (miRBase Accession No. MIMAT0022938) described in sequence number 8, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Lui WO et al., 2007, Cancer Res, Vol. 67, pp. 6031-6043. Additionally, "hsa-miR-937-5p" is known as a precursor of "hsa-mir-937" (miRBase Accession No. MI0005759, sequence number 258), which takes a hairpin-like structure.
[0123] As used in this specification, the terms "hsa-miR-4675 gene" or "hsa-miR-4675" include the hsa-miR-4675 gene (miRBase Accession No. MIMAT0019757) described in sequence number 9, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4675" is known as a precursor of "hsa-mir-4675" (miRBase Accession No. MI0017306, sequence number 259), which takes a hairpin-like structure.
[0124] As used in this specification, the terms "hsa-miR-6795-5p gene" or "hsa-miR-6795-5p" include the hsa-miR-6795-5p gene (miRBase Accession No. MIMAT0027490) as described in sequence number 10, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6795-5p" is known as a precursor of "hsa-mir-6795" (miRBase Accession No. MI0022640, sequence number 260), which takes a hairpin-like structure.
[0125] The terms "hsa-miR-4731-5p gene" or "hsa-miR-4731-5p" as used in this specification include the hsa-miR-4731-5p gene described in sequence number 11 (miRBase Accession No. MIMAT0019853), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4731-5p" is known as a precursor of "hsa-mir-4731" (miRBase Accession No. MI0017368, sequence number 261), which takes a hairpin-like structure.
[0126] As used in this specification, the terms "hsa-miR-5090 gene" or "hsa-miR-5090" include the hsa-miR-5090 gene described in sequence number 12 (miRBase Accession No. MIMAT0021082), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ding N et al., 2011, J Radiat Res, Vol. 52, pp. 425-432. Additionally, "hsa-miR-5090" is known as a precursor, "hsa-mir-5090" (miRBase Accession No. MI0017979, sequence number 262), which takes a hairpin-like structure.
[0127] The terms "hsa-miR-3620-5p gene" or "hsa-miR-3620-5p" as used in this specification include the hsa-miR-3620-5p gene described in sequence number 13 (miRBase Accession No. MIMAT0022967), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. Additionally, "hsa-miR-3620-5p" is known as a precursor, "hsa-mir-3620" (miRBase Accession No. MI0016011, sequence number 263), which takes a hairpin-like structure.
[0128] The terms "hsa-miR-1343-5p gene" or "hsa-miR-1343-5p" as used in this specification include the hsa-miR-1343-5p gene (miRBase Accession No. MIMAT0027038) described in sequence number 14, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-1343-5p" is known as a precursor of "hsa-mir-1343" (miRBase Accession No. MI0017320, sequence number 264), which takes a hairpin-like structure.
[0129] The terms "hsa-miR-6717-5p gene" or "hsa-miR-6717-5p" as used in this specification include the hsa-miR-6717-5p gene described in sequence number 15 (miRBase Accession No. MIMAT0025846), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Additionally, "hsa-miR-6717-5p" is known as a precursor of "hsa-mir-6717" (miRBase Accession No. MI0022551, sequence number 265), which takes a hairpin-like structure.
[0130] As used in this specification, the terms "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" include the hsa-miR-6825-5p gene (miRBase Accession No. MIMAT0027550) as described in sequence number 16, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6825-5p" is known as a precursor of "hsa-mir-6825" (miRBase Accession No. MI0022670, sequence number 266), which takes a hairpin-like structure.
[0131] As used in this specification, the terms "hsa-miR-6738-5p gene" or "hsa-miR-6738-5p" include the hsa-miR-6738-5p gene described in sequence number 17 (miRBase Accession No. MIMAT0027377), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6738-5p" is known as a precursor of "hsa-mir-6738" (miRBase Accession No. MI0022583, sequence number 267), which takes a hairpin-like structure.
[0132] The terms "hsa-miR-6769a-5p gene" or "hsa-miR-6769a-5p" as used in this specification include the hsa-miR-6769a-5p gene (miRBase Accession No. MIMAT0027438) as described in sequence number 18, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6769a-5p" is known as a precursor of "hsa-mir-6769a" (miRBase Accession No. MI0022614, sequence number 268), which takes a hairpin-like structure.
[0133] The terms "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" as used in this specification include the hsa-miR-4728-5p gene described in sequence number 19 (miRBase Accession No. MIMAT0019849), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4728-5p" is known as a precursor of "hsa-mir-4728" (miRBase Accession No. MI0017365, sequence number 269), which takes a hairpin-like structure.
[0134] The terms "hsa-miR-652-5p gene" or "hsa-miR-652-5p" as used in this specification include the hsa-miR-652-5p gene described in sequence number 20 (miRBase Accession No. MIMAT0022709), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Additionally, "hsa-miR-652-5p" is known as a hairpin-shaped precursor, "hsa-mir-652" (miRBase Accession No. MI0003667, sequence number 270).
[0135] As used in this specification, the terms "hsa-miR-4257 gene" or "hsa-miR-4257" include the hsa-miR-4257 gene described in sequence number 21 (miRBase Accession No. MIMAT0016878), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Additionally, "hsa-miR-4257" is known as a precursor of "hsa-mir-4257" (miRBase Accession No. MI0015856, sequence number 271), which takes a hairpin-like structure.
[0136] The terms "hsa-miR-6785-5p gene" or "hsa-miR-6785-5p" as used in this specification include the hsa-miR-6785-5p gene described in sequence number 22 (miRBase Accession No. MIMAT0027470), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6785-5p" is known as a hairpin-like precursor, "hsa-mir-6785" (miRBase Accession No. MI0022630, sequence number 272).
[0137] The terms “hsa-miR-7110-5p gene” or “hsa-miR-7110-5p” as used in this specification include the hsa-miR-7110-5p gene (miRBase Accession No. MIMAT0028117) described in sequence number 23, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, “hsa-miR-7110-5p” is known as a precursor of “hsa-mir-7110” (miRBase Accession No. MI0022961, sequence number 273), which takes a hairpin-like structure.
[0138] The terms "hsa-miR-6887-5p gene" or "hsa-miR-6887-5p" as used in this specification include the hsa-miR-6887-5p gene (miRBase Accession No. MIMAT0027674) described in sequence number 24, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6887-5p" is known as a precursor of "hsa-mir-6887" (miRBase Accession No. MI0022734, sequence number 274), which takes a hairpin-like structure.
[0139] The terms "hsa-miR-887-3p gene" or "hsa-miR-887-3p" as used in this specification include the hsa-miR-887-3p gene described in sequence number 25 (miRBase Accession No. MIMAT0004951), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Additionally, "hsa-miR-887-3p" is known as a hairpin-like precursor, "hsa-mir-887" (miRBase Accession No. MI0005562, sequence number 275).
[0140] The terms "hsa-miR-1228-5p gene" or "hsa-miR-1228-5p" as used in this specification include the hsa-miR-1228-5p gene (miRBase Accession No. MIMAT0005582) described in sequence number 26, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Additionally, "hsa-miR-1228-5p" is known as a precursor of "hsa-mir-1228" (miRBase Accession No. MI0006318, sequence number 276), which takes a hairpin-like structure.
[0141] As used in this specification, the terms "hsa-miR-5572 gene" or "hsa-miR-5572" include the hsa-miR-5572 gene described in sequence number 27 (miRBase Accession No. MIMAT0022260), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Tandon M et al., 2012, Oral Dis, Vol. 18, pp. 127-131. Additionally, "hsa-miR-5572" is known as a precursor of "hsa-mir-5572" (miRBase Accession No. MI0019117, sequence number 277), which takes a hairpin-like structure.
[0142] The terms "hsa-miR-6782-5p gene" or "hsa-miR-6782-5p" as used in this specification include the hsa-miR-6782-5p gene (miRBase Accession No. MIMAT0027464) as described in sequence number 28, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6782-5p" is known as a precursor of "hsa-mir-6782" (miRBase Accession No. MI0022627, sequence number 278), which takes a hairpin-like structure.
[0143] As used in this specification, the terms "hsa-miR-4298 gene" or "hsa-miR-4298" include the hsa-miR-4298 gene described in sequence number 29 (miRBase Accession No. MIMAT0016852), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Additionally, "hsa-miR-4298" is known as a precursor, "hsa-mir-4298" (miRBase Accession No. MI0015830, sequence number 279), which takes a hairpin-like structure.
[0144] As used in this specification, the terms "hsa-miR-6786-5p gene" or "hsa-miR-6786-5p" include the hsa-miR-6786-5p gene (miRBase Accession No. MIMAT0027472) described in sequence number 30, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6786-5p" is known as a precursor of "hsa-mir-6786" (miRBase Accession No. MI0022631, sequence number 280), which takes a hairpin-like structure.
[0145] The terms "hsa-miR-5010-5p gene" or "hsa-miR-5010-5p" as used in this specification include the hsa-miR-5010-5p gene (miRBase Accession No. MIMAT0021043) described in sequence number 31, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Hansen TB et al., 2011, RNA Biol, Vol. 8, pp. 378-383. Additionally, "hsa-miR-5010-5p" is known as a precursor, "hsa-mir-5010" (miRBase Accession No. MI0017878, sequence number 281), which takes a hairpin-like structure.
[0146] As used in this specification, the terms "hsa-miR-6087 gene" or "hsa-miR-6087" include the hsa-miR-6087 gene described in sequence number 32 (miRBase Accession No. MIMAT0023712), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Additionally, "hsa-miR-6087" is known as a precursor, and a hairpin-like structure, "hsa-mir-6087" (miRBase Accession No. MI0020364, sequence number 282), is also known.
[0147] The terms “hsa-miR-6765-5p gene” or “hsa-miR-6765-5p” as used in this specification include the hsa-miR-6765-5p gene (miRBase Accession No. MIMAT0027430) described in sequence number 33, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, “hsa-miR-6765-5p” is known as a precursor of “hsa-mir-6765” (miRBase Accession No. MI0022610, sequence number 283), which takes a hairpin-like structure.
[0148] The terms "hsa-miR-6732-5p gene" or "hsa-miR-6732-5p" as used in this specification include the hsa-miR-6732-5p gene described in sequence number 34 (miRBase Accession No. MIMAT0027365), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6732-5p" is known as a precursor of "hsa-mir-6732" (miRBase Accession No. MI0022577, sequence number 284), which takes a hairpin-like structure.
[0149] The terms "hsa-miR-6787-5p gene" or "hsa-miR-6787-5p" as used in this specification include the hsa-miR-6787-5p gene described in sequence number 35 (miRBase Accession No. MIMAT0027474), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6787-5p" is known as a hairpin-like precursor, "hsa-mir-6787" (miRBase Accession No. MI0022632, sequence number 285).
[0150] The terms "hsa-miR-6737-5p gene" or "hsa-miR-6737-5p" as used in this specification include the hsa-miR-6737-5p gene (miRBase Accession No. MIMAT0027375) described in sequence number 36, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6737-5p" is known as a hairpin-like precursor, "hsa-mir-6737" (miRBase Accession No. MI0022582, sequence number 286).
[0151] The terms "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" as used in this specification include the hsa-miR-128-2-5p gene described in sequence number 37 (miRBase Accession No. MIMAT0031095), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Additionally, "hsa-miR-128-2-5p" is known as a precursor, and its hairpin-like structure is known as "hsa-mir-128-2" (miRBase Accession No. MI0000727, sequence number 287).
[0152] As used in this specification, the terms "hsa-miR-4270 gene" or "hsa-miR-4270" include the hsa-miR-4270 gene (miRBase Accession No. MIMAT0016900) described in sequence number 38, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Additionally, "hsa-miR-4270" is known as a precursor, and a hairpin-like structure, "hsa-mir-4270" (miRBase Accession No. MI0015878, sequence number 288), is also known.
[0153] The terms "hsa-miR-6861-5p gene" or "hsa-miR-6861-5p" as used in this specification include the hsa-miR-6861-5p gene (miRBase Accession No. MIMAT0027623) described in sequence number 39, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6861-5p" is known as a precursor of "hsa-mir-6861" (miRBase Accession No. MI0022708, sequence number 289), which takes a hairpin-like structure.
[0154] As used in this specification, the terms "hsa-miR-6756-5p gene" or "hsa-miR-6756-5p" include the hsa-miR-6756-5p gene (miRBase Accession No. MIMAT0027412) as described in sequence number 40, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6756-5p" is known as a precursor of "hsa-mir-6756" (miRBase Accession No. MI0022601, sequence number 290), which takes a hairpin-like structure.
[0155] The terms "hsa-miR-1229-5p gene" or "hsa-miR-1229-5p" as used in this specification include the hsa-miR-1229-5p gene (miRBase Accession No. MIMAT0022942) described in sequence number 41, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Additionally, "hsa-miR-1229-5p" is known as a precursor of "hsa-mir-1229" (miRBase Accession No. MI0006319, sequence number 291), which takes a hairpin-like structure.
[0156] As used in this specification, the terms "hsa-miR-6891-5p gene" or "hsa-miR-6891-5p" include the hsa-miR-6891-5p gene (miRBase Accession No. MIMAT0027682) as described in sequence number 42, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6891-5p" is known as a precursor of "hsa-mir-6891" (miRBase Accession No. MI0022738, sequence number 292), which takes a hairpin-like structure.
[0157] The terms "hsa-miR-6848-5p gene" or "hsa-miR-6848-5p" as used in this specification include the hsa-miR-6848-5p gene (miRBase Accession No. MIMAT0027596) described in sequence number 43, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6848-5p" is known as a precursor of "hsa-mir-6848" (miRBase Accession No. MI0022694, sequence number 293), which takes a hairpin-like structure.
[0158] The terms "hsa-miR-1237-5p gene" or "hsa-miR-1237-5p" as used in this specification include the hsa-miR-1237-5p gene (miRBase Accession No. MIMAT0022946) described in sequence number 44, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Additionally, "hsa-miR-1237-5p" is known as a precursor of "hsa-mir-1237" (miRBase Accession No. MI0006327, sequence number 294), which takes a hairpin-like structure.
[0159] The terms "hsa-miR-30c-1-3p gene" or "hsa-miR-30c-1-3p" as used in this specification include the hsa-miR-30c-1-3p gene (miRBase Accession No. MIMAT0004674) described in sequence number 45, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Additionally, "hsa-miR-30c-1-3p" is known as a precursor, "hsa-mir-30c-1" (miRBase Accession No. MI0000736, sequence number 295), which takes a hairpin-like structure.
[0160] The terms "hsa-miR-1233-5p gene" or "hsa-miR-1233-5p" as used in this specification include the hsa-miR-1233-5p gene described in sequence number 46 (miRBase Accession No. MIMAT0022943), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Additionally, "hsa-miR-1233-5p" is known as a precursor in hairpin-like structures, namely "hsa-mir-1233-1" and "hsa-mir-1233-2" (miRBase Accession Nos. MI0006323, MI0015973, sequence numbers 296 and 297).
[0161] The terms "hsa-miR-211-3p gene" or "hsa-miR-211-3p" as used in this specification include the hsa-miR-211-3p gene described in sequence number 47 (miRBase Accession No. MIMAT0022694), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Lim LP et al., 2003, Science, Vol. 299, p. 1540. Additionally, "hsa-miR-211-3p" is known as a hairpin-like precursor, "hsa-mir-211" (miRBase Accession No. MI0000287, sequence number 298).
[0162] The terms "hsa-miR-4758-5p gene" or "hsa-miR-4758-5p" as used in this specification include the hsa-miR-4758-5p gene (miRBase Accession No. MIMAT0019903) as described in sequence number 48, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4758-5p" is known as a precursor of "hsa-mir-4758" (miRBase Accession No. MI0017399, sequence number 299), which takes a hairpin-like structure.
[0163] As used in this specification, the terms "hsa-miR-614 gene" or "hsa-miR-614" include the hsa-miR-614 gene described in sequence number 49 (miRBase Accession No. MIMAT0003282), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Cummins JM et al., 2006, Proc Natl Acad SciUSA, Vol. 103, pp. 3687-3692. Additionally, "hsa-miR-614" is known as a hairpin-shaped precursor, "hsa-mir-614" (miRBase Accession No. MI0003627, sequence number 300).
[0164] The terms "hsa-miR-6746-5p gene" or "hsa-miR-6746-5p" as used in this specification include the hsa-miR-6746-5p gene described in sequence number 50 (miRBase Accession No. MIMAT0027392), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6746-5p" is known as a precursor of "hsa-mir-6746" (miRBase Accession No. MI0022591, sequence number 301), which takes a hairpin-like structure.
[0165] As used in this specification, the terms "hsa-miR-1915-5p gene" or "hsa-miR-1915-5p" include the hsa-miR-1915-5p gene (miRBase Accession No. MIMAT0007891) as described in sequence number 51, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Additionally, "hsa-miR-1915-5p" is known as a precursor of "hsa-mir-1915" (miRBase Accession No. MI0008336, sequence number 302), which takes a hairpin-like structure.
[0166] As used in this specification, the terms "hsa-miR-4688 gene" or "hsa-miR-4688" include the hsa-miR-4688 gene described in sequence number 52 (miRBase Accession No. MIMAT0019777), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4688" is known as a hairpin-like precursor, "hsa-mir-4688" (miRBase Accession No. MI0017321, sequence number 303).
[0167] As used in this specification, the terms "hsa-miR-3917 gene" or "hsa-miR-3917" include the hsa-miR-3917 gene described in sequence number 53 (miRBase Accession No. MIMAT0018191), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Additionally, "hsa-miR-3917" is known as a precursor, "hsa-mir-3917" (miRBase Accession No. MI0016423, sequence number 304), which takes a hairpin-like structure.
[0168] As used in this specification, the terms "hsa-miR-5787 gene" or "hsa-miR-5787" include the hsa-miR-5787 gene (miRBase Accession No. MIMAT0023252) described in sequence number 54, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Yoo H et al., 2011, Biochem Biophys ResCommun, Vol. 415, pp. 567-572. Additionally, "hsa-miR-5787" is known as a precursor of "hsa-mir-5787" (miRBase Accession No. MI0019797, sequence number 305), which takes a hairpin-like structure.
[0169] The terms "hsa-miR-4632-5p gene" or "hsa-miR-4632-5p" as used in this specification include the hsa-miR-4632-5p gene (miRBase Accession No. MIMAT0022977) described in sequence number 55, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4632-5p" is known as a precursor of "hsa-mir-4632" (miRBase Accession No. MI0017259, sequence number 306), which takes a hairpin-like structure.
[0170] As used in this specification, the terms "hsa-miR-6126 gene" or "hsa-miR-6126" include the hsa-miR-6126 gene described in sequence number 56 (miRBase Accession No. MIMAT0024599), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. Additionally, "hsa-miR-6126" is known as a precursor, "hsa-mir-6126" (miRBase Accession No. MI0021260, sequence number 307), which takes a hairpin-like structure.
[0171] The terms "hsa-miR-135a-3p gene" or "hsa-miR-135a-3p" as used in this specification include the hsa-miR-135a-3p gene described in sequence number 57 (miRBase Accession No. MIMAT0004595), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Lagos-Quintana M et al., 2002, CurrBiol, Vol. 12, pp. 735-739. Additionally, "hsa-miR-135a-3p" is known as a precursor, "hsa-mir-135a-1" (miRBase Accession No. MI0000452, sequence number 308), which takes a hairpin-like structure.
[0172] As used in this specification, the terms "hsa-miR-8063 gene" or "hsa-miR-8063" include the hsa-miR-8063 gene described in sequence number 58 (miRBase Accession No. MIMAT0030990), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. Additionally, "hsa-miR-8063" is known as a precursor, "hsa-mir-8063" (miRBase Accession No. MI0025899, sequence number 309), which takes a hairpin-like structure.
[0173] As used in this specification, the terms "hsa-miR-5698 gene" or "hsa-miR-5698" include the hsa-miR-5698 gene described in sequence number 59 (miRBase Accession No. MIMAT0022491), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Watahiki A et al., 2011, PLoS One, Vol. 6, e24950. Additionally, "hsa-miR-5698" is known as a precursor, "hsa-mir-5698" (miRBase Accession No. MI0019305, sequence number 310), which takes a hairpin-like structure.
[0174] As used in this specification, the terms "hsa-miR-6089 gene" or "hsa-miR-6089" include the hsa-miR-6089 gene described in sequence number 60 (miRBase Accession No. MIMAT0023714), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Additionally, "hsa-miR-6089" is known as a precursor, and its hairpin-like structures are known as "hsa-mir-6089-1, hsa-mir-6089-2" (miRBase Accession Nos. MI0020366, MI0023563, sequence numbers 311, 312).
[0175] As used in this specification, the terms "hsa-miR-498 gene" or "hsa-miR-498" include the hsa-miR-498 gene described in sequence number 61 (miRBase Accession No. MIMAT0002824), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Bentwich I et al., 2005, Nat Genet, Vol. 37, pp. 766-770. Additionally, "hsa-miR-498" is known as a hairpin-like precursor, "hsa-mir-498" (miRBase Accession No. MI0003142, sequence number 313).
[0176] The terms "hsa-miR-296-3p gene" or "hsa-miR-296-3p" as used in this specification include the hsa-miR-296-3p gene described in sequence number 62 (miRBase Accession No. MIMAT0004679), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Houbavy HB et al., 2003, Dev Cell, Vol. 5, pp. 351-358. Additionally, "hsa-miR-296-3p" is known as a precursor, "hsa-mir-296" (miRBase Accession No. MI0000747, sequence number 314), which takes a hairpin-like structure.
[0177] As used in this specification, the terms "hsa-miR-4419b gene" or "hsa-miR-4419b" include the hsa-miR-4419b gene described in sequence number 63 (miRBase Accession No. MIMAT0019034), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4419b" is known as a precursor of "hsa-mir-4419b" (miRBase Accession No. MI0016861, sequence number 315), which takes a hairpin-like structure.
[0178] The terms "hsa-miR-6802-5p gene" or "hsa-miR-6802-5p" as used in this specification include the hsa-miR-6802-5p gene (miRBase Accession No. MIMAT0027504) described in sequence number 64, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6802-5p" is known as a precursor of "hsa-mir-6802" (miRBase Accession No. MI0022647, sequence number 316), which takes a hairpin-like structure.
[0179] The terms “hsa-miR-6829-5p gene” or “hsa-miR-6829-5p” as used in this specification include the hsa-miR-6829-5p gene (miRBase Accession No. MIMAT0027558) described in sequence number 65, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, “hsa-miR-6829-5p” is known as a precursor of “hsa-mir-6829” (miRBase Accession No. MI0022674, sequence number 317), which takes a hairpin-like structure.
[0180] The terms “hsa-miR-6803-5p gene” or “hsa-miR-6803-5p” as used in this specification include the hsa-miR-6803-5p gene (miRBase Accession No. MIMAT0027506) described in sequence number 66, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, “hsa-miR-6803-5p” is known as a precursor of “hsa-mir-6803” (miRBase Accession No. MI0022648, sequence number 318), which takes a hairpin-like structure.
[0181] The terms "hsa-miR-1199-5p gene" or "hsa-miR-1199-5p" as used in this specification include the hsa-miR-1199-5p gene (miRBase Accession No. MIMAT0031119) described in sequence number 67, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Salvi A et al., 2013, Int J Oncol, Vol. 42, pp. 391-402. Additionally, "hsa-miR-1199-5p" is known as a precursor of "hsa-mir-1199" (miRBase Accession No. MI0020340, sequence number 319), which takes a hairpin-like structure.
[0182] The terms "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" as used in this specification include the hsa-miR-6840-3p gene (miRBase Accession No. MIMAT0027583) as described in sequence number 68, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6840-3p" is known as a precursor of "hsa-mir-6840" (miRBase Accession No. MI0022686, sequence number 320), which takes a hairpin-like structure.
[0183] The terms "hsa-miR-6752-5p gene" or "hsa-miR-6752-5p" as used in this specification include the hsa-miR-6752-5p gene (miRBase Accession No. MIMAT0027404) described in sequence number 69, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6752-5p" is known as a precursor of "hsa-mir-6752" (miRBase Accession No. MI0022597, sequence number 321), which takes a hairpin-like structure.
[0184] The terms "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" as used in this specification include the hsa-miR-6798-5p gene described in sequence number 70 (miRBase Accession No. MIMAT0027496), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6798-5p" is known as a precursor of "hsa-mir-6798" (miRBase Accession No. MI0022643, sequence number 322), which takes a hairpin-like structure.
[0185] As used in this specification, the terms "hsa-miR-6131 gene" or "hsa-miR-6131" include the hsa-miR-6131 gene described in sequence number 71 (miRBase Accession No. MIMAT0024615), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Dannemann M et al., 2012, Genome Biol Evol, Vol. 4, pp. 552-564. Additionally, "hsa-miR-6131" is known as a precursor, "hsa-mir-6131" (miRBase Accession No. MI0021276, sequence number 323), which takes a hairpin-like structure.
[0186] The terms "hsa-miR-4667-5p gene" or "hsa-miR-4667-5p" as used in this specification include the hsa-miR-4667-5p gene (miRBase Accession No. MIMAT0019743) described in sequence number 72, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4667-5p" is known as a hairpin-like precursor, "hsa-mir-4667" (miRBase Accession No. MI0017297, sequence number 324).
[0187] The terms "hsa-miR-6510-5p gene" or "hsa-miR-6510-5p" as used in this specification include the hsa-miR-6510-5p gene (miRBase Accession No. MIMAT0025476) described in sequence number 73, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Joyce CE et al., 2011, Hum MolGenet, Vol. 20, pp. 4025-4040. Additionally, "hsa-miR-6510-5p" is known as a precursor of "hsa-mir-6510" (miRBase Accession No. MI0022222, sequence number 325), which takes a hairpin-like structure.
[0188] The terms "hsa-miR-4690-5p gene" or "hsa-miR-4690-5p" as used in this specification include the hsa-miR-4690-5p gene (miRBase Accession No. MIMAT0019779) described in sequence number 74, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4690-5p" is known as a precursor of "hsa-mir-4690" (miRBase Accession No. MI0017323, sequence number 326), which takes a hairpin-like structure.
[0189] As used in this specification, the terms "hsa-miR-920 gene" or "hsa-miR-920" include the hsa-miR-920 gene described in sequence number 75 (miRBase Accession No. MIMAT0004970), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Novotny GW et al., 2007, Int J Androl, Vol. 30, pp. 316-326. Additionally, "hsa-miR-920" is known as a precursor, "hsa-mir-920" (miRBase Accession No. MI0005712, sequence number 327), which takes a hairpin-like structure.
[0190] The terms "hsa-miR-23b-3p gene" or "hsa-miR-23b-3p" as used in this specification include the hsa-miR-23b-3p gene (miRBase Accession No. MIMAT0000418) described in sequence number 76, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Lagos-Quintana M et al., 2002, CurrBiol, Vol. 12, pp. 735-739. Additionally, "hsa-miR-23b-3p" is known as a precursor of "hsa-mir-23b" (miRBase Accession No. MI0000439, sequence number 328), which takes a hairpin-like structure.
[0191] As used in this specification, the terms "hsa-miR-4448 gene" or "hsa-miR-4448" include the hsa-miR-4448 gene described in sequence number 77 (miRBase Accession No. MIMAT0018967), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4448" is known as a hairpin-like precursor, "hsa-mir-4448" (miRBase Accession No. MI0016791, sequence number 329).
[0192] As used in this specification, the terms "hsa-miR-2110 gene" or "hsa-miR-2110" include the hsa-miR-2110 gene (miRBase Accession No. MIMAT0010133) as described in sequence number 78, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Zhu JY et al., 2009, J Virol, Vol. 83, pp. 3333-3341. Additionally, "hsa-miR-2110" is known as a precursor, "hsa-mir-2110" (miRBase Accession No. MI0010629, sequence number 330), which takes a hairpin-like structure.
[0193] As used in this specification, the terms "hsa-miR-4706 gene" or "hsa-miR-4706" include the hsa-miR-4706 gene described in sequence number 79 (miRBase Accession No. MIMAT0019806), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4706" is known as a precursor, "hsa-mir-4706" (miRBase Accession No. MI0017339, sequence number 331), which takes a hairpin-like structure.
[0194] The terms "hsa-miR-7845-5p gene" or "hsa-miR-7845-5p" as used in this specification include the hsa-miR-7845-5p gene described in sequence number 80 (miRBase Accession No. MIMAT0030420), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Additionally, "hsa-miR-7845-5p" is known as a precursor of "hsa-mir-7845" (miRBase Accession No. MI0025515, sequence number 332), which takes a hairpin-like structure.
[0195] The terms "hsa-miR-6808-5p gene" or "hsa-miR-6808-5p" as used in this specification include the hsa-miR-6808-5p gene described in sequence number 81 (miRBase Accession No. MIMAT0027516), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6808-5p" is known as a hairpin-like precursor, "hsa-mir-6808" (miRBase Accession No. MI0022653, sequence number 333).
[0196] As used in this specification, the terms "hsa-miR-4447 gene" or "hsa-miR-4447" include the hsa-miR-4447 gene described in sequence number 82 (miRBase Accession No. MIMAT0018966), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4447" is known as a hairpin-like precursor, "hsa-mir-4447" (miRBase Accession No. MI0016790, sequence number 334).
[0197] The terms "hsa-miR-6869-5p gene" or "hsa-miR-6869-5p" as used in this specification include the hsa-miR-6869-5p gene (miRBase Accession No. MIMAT0027638) as described in sequence number 83, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6869-5p" is known as a precursor of "hsa-mir-6869" (miRBase Accession No. MI0022716, sequence number 335), which takes a hairpin-like structure.
[0198] The terms "hsa-miR-1908-5p gene" or "hsa-miR-1908-5p" as used in this specification include the hsa-miR-1908-5p gene (miRBase Accession No. MIMAT0007881) as described in sequence number 84, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Additionally, "hsa-miR-1908-5p" is known as a hairpin-like precursor, "hsa-mir-1908" (miRBase Accession No. MI0008329, sequence number 336).
[0199] As used in this specification, the terms "hsa-miR-6729-5p gene" or "hsa-miR-6729-5p" include the hsa-miR-6729-5p gene (miRBase Accession No. MIMAT0027359) as described in sequence number 85, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6729-5p" is known as a precursor of "hsa-mir-6729" (miRBase Accession No. MI0022574, sequence number 337), which takes a hairpin-like structure.
[0200] The terms "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" as used in this specification include the hsa-miR-5195-3p gene (miRBase Accession No. MIMAT0021127) as described in sequence number 86, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Schotte D et al., 2011, Leukemia, Vol. 25, pp. 1389-1399. Additionally, "hsa-miR-5195-3p" is known as a hairpin-like precursor, "hsa-mir-5195" (miRBase Accession No. MI0018174, sequence number 338).
[0201] As used in this specification, the terms "hsa-miR-638 gene" or "hsa-miR-638" include the hsa-miR-638 gene described in sequence number 87 (miRBase Accession No. MIMAT0003308), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Cummins JM et al., 2006, Proc Natl Acad SciUSA, Vol. 103, pp. 3687-3692. Additionally, "hsa-miR-638" is known as a hairpin-shaped precursor, "hsa-mir-638" (miRBase Accession No. MI0003653, sequence number 339).
[0202] As used in this specification, the terms "hsa-miR-6125 gene" or "hsa-miR-6125" include the hsa-miR-6125 gene described in sequence number 88 (miRBase Accession No. MIMAT0024598), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. Additionally, "hsa-miR-6125" is known as a precursor of "hsa-mir-6125" (miRBase Accession No. MI0021259, sequence number 340), which takes a hairpin-like structure.
[0203] As used in this specification, the terms "hsa-miR-3178 gene" or "hsa-miR-3178" include the hsa-miR-3178 gene described in sequence number 89 (miRBase Accession No. MIMAT0015055), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Additionally, "hsa-miR-3178" is known as a hairpin-like precursor, "hsa-mir-3178" (miRBase Accession No. MI0014212, sequence number 341).
[0204] As used in this specification, the terms "hsa-miR-3196 gene" or "hsa-miR-3196" include the hsa-miR-3196 gene described in sequence number 90 (miRBase Accession No. MIMAT0015080), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Additionally, "hsa-miR-3196" is known as a precursor, "hsa-mir-3196" (miRBase Accession No. MI0014241, sequence number 342), which takes a hairpin-like structure.
[0205] As used in this specification, the terms "hsa-miR-8069 gene" or "hsa-miR-8069" include the hsa-miR-8069 gene described in sequence number 91 (miRBase Accession No. MIMAT0030996), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. Additionally, "hsa-miR-8069" is known as a precursor, and its hairpin-like structures are known as "hsa-mir-8069-1, hsa-mir-8069-2" (miRBase Accession Nos. MI0025905, MI0031519, sequence numbers 343, 344).
[0206] The terms "hsa-miR-4723-5p gene" or "hsa-miR-4723-5p" as used in this specification include the hsa-miR-4723-5p gene (miRBase Accession No. MIMAT0019838) as described in sequence number 92, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4723-5p" is known as a precursor of "hsa-mir-4723" (miRBase Accession No. MI0017359, sequence number 345), which takes a hairpin-like structure.
[0207] The terms "hsa-miR-4746-3p gene" or "hsa-miR-4746-3p" as used in this specification include the hsa-miR-4746-3p gene (miRBase Accession No. MIMAT0019881) as described in sequence number 93, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4746-3p" is known as a hairpin-like precursor, "hsa-mir-4746" (miRBase Accession No. MI0017385, sequence number 346).
[0208] As used in this specification, the terms "hsa-miR-4689 gene" or "hsa-miR-4689" include the hsa-miR-4689 gene described in sequence number 94 (miRBase Accession No. MIMAT0019778), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4689" is known as a hairpin-like precursor, "hsa-mir-4689" (miRBase Accession No. MI0017322, sequence number 347).
[0209] As used in this specification, the terms "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" include the hsa-miR-6816-5p gene (miRBase Accession No. MIMAT0027532) as described in sequence number 95, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6816-5p" is known as a precursor of "hsa-mir-6816" (miRBase Accession No. MI0022661, sequence number 348), which takes a hairpin-like structure.
[0210] The terms "hsa-miR-6757-5p gene" or "hsa-miR-6757-5p" as used in this specification include the hsa-miR-6757-5p gene (miRBase Accession No. MIMAT0027414) as described in sequence number 96, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6757-5p" is known as a hairpin-like precursor, "hsa-mir-6757" (miRBase Accession No. MI0022602, sequence number 349).
[0211] The terms "hsa-miR-7109-5p gene" or "hsa-miR-7109-5p" as used in this specification include the hsa-miR-7109-5p gene described in sequence number 97 (miRBase Accession No. MIMAT0028115), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-7109-5p" is known as a precursor of "hsa-mir-7109" (miRBase Accession No. MI0022960, sequence number 350), which takes a hairpin-like structure.
[0212] The terms "hsa-miR-6724-5p gene" or "hsa-miR-6724-5p" as used in this specification include the hsa-miR-6724-5p gene (miRBase Accession No. MIMAT0025856) as described in sequence number 98, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. In addition, "hsa-miR-6724-5p" is known as a precursor, and "hsa-mir-6724-1, hsa-mir-6724-2, hsa-mir-6724-3, hsa-mir-6724-4" with hairpin-like structures are known (miRBaseAccession No. MI0022559, MI0031516, MI0031517, MI0031518, serial numbers 351, 352, 353, 354).
[0213] The terms "hsa-miR-1225-3p gene" or "hsa-miR-1225-3p" as used in this specification include the hsa-miR-1225-3p gene (miRBase Accession No. MIMAT0005573) as described in sequence number 99, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Additionally, "hsa-miR-1225-3p" is known as a precursor of "hsa-mir-1225" (miRBase Accession No. MI0006311, sequence number 355), which takes a hairpin-like structure.
[0214] The terms "hsa-miR-6875-5p gene" or "hsa-miR-6875-5p" as used in this specification include the hsa-miR-6875-5p gene described in sequence number 100 (miRBase Accession No. MIMAT0027650), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6875-5p" is known as a hairpin-structured precursor, "hsa-mir-6875" (miRBase Accession No. MI0022722, sequence number 356).
[0215] The terms "hsa-miR-7108-5p gene" or "hsa-miR-7108-5p" as used in this specification include the hsa-miR-7108-5p gene described in sequence number 101 (miRBase Accession No. MIMAT0028113), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-7108-5p" is known as a precursor of "hsa-mir-7108" (miRBase Accession No. MI0022959, sequence number 357), which adopts a hairpin-like structure.
[0216] As used in this specification, the terms "hsa-miR-4508 gene" or "hsa-miR-4508" include the hsa-miR-4508 gene described in sequence number 102 (miRBase Accession No. MIMAT0019045), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4508" is known as a precursor, "hsa-mir-4508" (miRBase Accession No. MI0016872, sequence number 358), which takes a hairpin-like structure.
[0217] As used in this specification, the terms "hsa-miR-6085 gene" or "hsa-miR-6085" include the hsa-miR-6085 gene described in sequence number 103 (miRBase Accession No. MIMAT0023710), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Voellenkle C et al., 2012, RNA, Vol. 18, pp. 472-484. Additionally, "hsa-miR-6085" is known as a precursor of "hsa-mir-6085" (miRBase Accession No. MI0020362, sequence number 359), which takes a hairpin-like structure.
[0218] The terms "hsa-miR-6779-5p gene" or "hsa-miR-6779-5p" as used in this specification include the hsa-miR-6779-5p gene (miRBase Accession No. MIMAT0027458) described in sequence number 104, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6779-5p" is known as a precursor of "hsa-mir-6779" (miRBase Accession No. MI0022624, sequence number 360), which takes a hairpin-like structure.
[0219] The terms "hsa-miR-642a-3p gene" or "hsa-miR-642a-3p" as used in this specification include the hsa-miR-642a-3p gene described in sequence number 105 (miRBase Accession No. MIMAT0020924), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Cummins JM et al., 2006, ProcNatl Acad Sci USA, Vol. 103, pp. 3687-3692. Additionally, "hsa-miR-642a-3p" is known as a hairpin-shaped precursor of "hsa-mir-642a" (miRBase Accession No. MI0003657, sequence number 361).
[0220] The terms "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" as used in this specification include the hsa-miR-4695-5p gene (miRBase Accession No. MIMAT0019788) described in sequence number 106, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4695-5p" is known as a hairpin-like precursor, "hsa-mir-4695" (miRBase Accession No. MI0017328, sequence number 362).
[0221] The terms "hsa-miR-7847-3p gene" or "hsa-miR-7847-3p" as used in this specification include the hsa-miR-7847-3p gene (miRBase Accession No. MIMAT0030422) described in sequence number 107, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Additionally, "hsa-miR-7847-3p" is known as a precursor of "hsa-mir-7847" (miRBase Accession No. MI0025517, sequence number 363), which takes a hairpin-like structure.
[0222] As used in this specification, the terms "hsa-miR-3197 gene" or "hsa-miR-3197" include the hsa-miR-3197 gene described in sequence number 108 (miRBase Accession No. MIMAT0015082), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Additionally, "hsa-miR-3197" is known as a precursor, "hsa-mir-3197" (miRBase Accession No. MI0014245, sequence number 364), which takes a hairpin-like structure.
[0223] The terms "hsa-miR-6769b-5p gene" or "hsa-miR-6769b-5p" as used in this specification include the hsa-miR-6769b-5p gene (miRBase Accession No. MIMAT0027620) as described in sequence number 109, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6769b-5p" is known as a precursor, "hsa-mir-6769b" (miRBase Accession No. MI0022706, sequence number 365), which takes a hairpin-like structure.
[0224] As used in this specification, the terms "hsa-miR-7641 gene" or "hsa-miR-7641" include the hsa-miR-7641 gene described in sequence number 110 (miRBase Accession No. MIMAT0029782), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Yoo JK et al., 2013, Arch Pharm Res, Vol. 36, pp. 353-358. Additionally, "hsa-miR-7641" is known as a precursor, and its hairpin-like structures are known as "hsa-mir-7641-1, hsa-mir-7641-2" (miRBase Accession Nos. MI0024975, MI0024976, sequence numbers 366, 367).
[0225] The terms "hsa-miR-187-5p gene" or "hsa-miR-187-5p" as used in this specification include the hsa-miR-187-5p gene described in sequence number 111 (miRBase Accession No. MIMAT0004561), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Lim LP et al., 2003, Science, Vol. 299, p. 1540. Additionally, "hsa-miR-187-5p" is known as a hairpin-like precursor, "hsa-mir-187" (miRBase Accession No. MI0000274, sequence number 368).
[0226] As used in this specification, the terms "hsa-miR-3185 gene" or "hsa-miR-3185" include the hsa-miR-3185 gene described in sequence number 112 (miRBase Accession No. MIMAT0015065), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Additionally, "hsa-miR-3185" is known as a precursor, "hsa-mir-3185" (miRBase Accession No. MI0014227, sequence number 369), which takes a hairpin-like structure.
[0227] As used in this specification, the terms "hsa-miR-2861 gene" or "hsa-miR-2861" include the hsa-miR-2861 gene described in sequence number 113 (miRBase Accession No. MIMAT0013802), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Li H et al., 2009, J Clin Invest, Vol. 119, pp. 3666-3677. Additionally, "hsa-miR-2861" is known as a precursor, "hsa-mir-2861" (miRBase Accession No. MI0013006, sequence number 370), which takes a hairpin-like structure.
[0228] The terms "hsa-miR-3940-5p gene" or "hsa-miR-3940-5p" as used in this specification include the hsa-miR-3940-5p gene (miRBase Accession No. MIMAT0019229) described in sequence number 114, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Additionally, "hsa-miR-3940-5p" is known as a precursor, "hsa-mir-3940" (miRBase Accession No. MI0016597, sequence number 371), which takes a hairpin-like structure.
[0229] As used in this specification, the terms "hsa-miR-1203 gene" or "hsa-miR-1203" include the hsa-miR-1203 gene described in sequence number 115 (miRBase Accession No. MIMAT0005866), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Marton S et al., 2008, Leukemia, Vol. 22, pp. 330-338. Additionally, "hsa-miR-1203" is known as a precursor, "hsa-mir-1203" (miRBase Accession No. MI0006335, sequence number 372), which takes a hairpin-like structure.
[0230] The terms "hsa-miR-615-5p gene" or "hsa-miR-615-5p" as used in this specification include the hsa-miR-615-5p gene (miRBase Accession No. MIMAT0004804) as described in sequence number 116, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Additionally, "hsa-miR-615-5p" is known as a hairpin-shaped precursor, "hsa-mir-615" (miRBase Accession No. MI0003628, sequence number 373).
[0231] The terms "hsa-miR-4787-5p gene" or "hsa-miR-4787-5p" as used in this specification include the hsa-miR-4787-5p gene (miRBase Accession No. MIMAT0019956) as described in sequence number 117, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4787-5p" is known as a hairpin-like precursor, "hsa-mir-4787" (miRBase Accession No. MI0017434, sequence number 374).
[0232] The terms "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" as used in this specification include the hsa-miR-1343-3p gene (miRBase Accession No. MIMAT0019776) as described in sequence number 118, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-1343-3p" is known as a hairpin-like precursor, "hsa-mir-1343" (miRBase Accession No. MI0017320, sequence number 375).
[0233] The terms "hsa-miR-6813-5p gene" or "hsa-miR-6813-5p" as used in this specification include the hsa-miR-6813-5p gene (miRBase Accession No. MIMAT0027526) as described in sequence number 119, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6813-5p" is known as a precursor of "hsa-mir-6813" (miRBase Accession No. MI0022658, sequence number 376), which takes a hairpin-like structure.
[0234] The terms "hsa-miR-1225-5p gene" or "hsa-miR-1225-5p" as used in this specification include the hsa-miR-1225-5p gene (miRBase Accession No. MIMAT0005572) as described in sequence number 120, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Berezikov E et al., 2007, MolCell, Vol. 28, pp. 328-336. Additionally, "hsa-miR-1225-5p" is known as a precursor of "hsa-mir-1225" (miRBase Accession No. MI0006311, sequence number 377), which takes a hairpin-like structure.
[0235] As used in this specification, the terms "hsa-miR-602 gene" or "hsa-miR-602" include the hsa-miR-602 gene described in sequence number 121 (miRBase Accession No. MIMAT0003270), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Cummins JM et al., 2006, Proc Natl Acad SciUSA, Vol. 103, pp. 3687-3692. Additionally, "hsa-miR-602" is known as a precursor, "hsa-mir-602" (miRBase Accession No. MI0003615, sequence number 378), which takes a hairpin-like structure.
[0236] As used in this specification, the terms "hsa-miR-4488 gene" or "hsa-miR-4488" include the hsa-miR-4488 gene described in sequence number 122 (miRBase Accession No. MIMAT0019022), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4488" is known as a precursor of "hsa-mir-4488" (miRBase Accession No. MI0016849, sequence number 379), which takes a hairpin-like structure.
[0237] The terms "hsa-miR-125a-3p gene" or "hsa-miR-125a-3p" as used in this specification include the hsa-miR-125a-3p gene (miRBase Accession No. MIMAT0004602) described in sequence number 123, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Additionally, "hsa-miR-125a-3p" is known as a precursor of "hsa-mir-125a" (miRBase Accession No. MI0000469, sequence number 380), which takes a hairpin-like structure.
[0238] As used in this specification, the terms "hsa-miR-5100 gene" or "hsa-miR-5100" include the hsa-miR-5100 gene described in sequence number 124 (miRBase Accession No. MIMAT0022259), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Tandon M et al., 2012, Oral Dis, Vol. 18, pp. 127-131. Additionally, "hsa-miR-5100" is known as a precursor, "hsa-mir-5100" (miRBase Accession No. MI0019116, sequence number 381), which takes a hairpin-like structure.
[0239] As used in this specification, the terms "hsa-miR-4294 gene" or "hsa-miR-4294" include the hsa-miR-4294 gene described in sequence number 125 (miRBase Accession No. MIMAT0016849), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Additionally, "hsa-miR-4294" is known as a precursor, "hsa-mir-4294" (miRBase Accession No. MI0015827, sequence number 382), which takes a hairpin-like structure.
[0240] As used in this specification, the terms "hsa-miR-1231 gene" or "hsa-miR-1231" include the hsa-miR-1231 gene described in sequence number 126 (miRBase Accession No. MIMAT0005586), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Additionally, "hsa-miR-1231" is known as a hairpin-like precursor, "hsa-mir-1231" (miRBase Accession No. MI0006321, sequence number 383).
[0241] The terms "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" as used in this specification include the hsa-miR-6765-3p gene (miRBase Accession No. MIMAT0027431) described in sequence number 127, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6765-3p" is known as a precursor of "hsa-mir-6765" (miRBase Accession No. MI0022610, sequence number 384), which takes a hairpin-like structure.
[0242] As used in this specification, the terms "hsa-miR-4442 gene" or "hsa-miR-4442" include the hsa-miR-4442 gene described in sequence number 128 (miRBase Accession No. MIMAT0018960), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4442" is known as a precursor of "hsa-mir-4442" (miRBase Accession No. MI0016785, sequence number 385), which takes a hairpin-like structure.
[0243] As used in this specification, the terms "hsa-miR-718 gene" or "hsa-miR-718" include the hsa-miR-718 gene described in sequence number 129 (miRBase Accession No. MIMAT0012735), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p39. Additionally, "hsa-miR-718" is known as a hairpin-like precursor, "hsa-mir-718" (miRBase Accession No. MI0012489, sequence number 386).
[0244] The terms "hsa-miR-6780b-5p gene" or "hsa-miR-6780b-5p" as used in this specification include the hsa-miR-6780b-5p gene (miRBase Accession No. MIMAT0027572) described in sequence number 130, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6780b-5p" is known as a precursor, "hsa-mir-6780b" (miRBase Accession No. MI0022681, sequence number 387), which takes a hairpin-like structure.
[0245] As used in this specification, the terms "hsa-miR-6090 gene" or "hsa-miR-6090" include the hsa-miR-6090 gene described in sequence number 131 (miRBase Accession No. MIMAT0023715), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Additionally, "hsa-miR-6090" is known as a precursor, "hsa-mir-6090" (miRBase Accession No. MI0020367, sequence number 388), which takes a hairpin-like structure.
[0246] The terms "hsa-miR-6845-5p gene" or "hsa-miR-6845-5p" as used in this specification include the hsa-miR-6845-5p gene (miRBase Accession No. MIMAT0027590) as described in sequence number 132, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6845-5p" is known as a precursor of "hsa-mir-6845" (miRBase Accession No. MI0022691, sequence number 389), which takes a hairpin-like structure.
[0247] As used in this specification, the terms "hsa-miR-4741 gene" or "hsa-miR-4741" include the hsa-miR-4741 gene described in sequence number 133 (miRBase Accession No. MIMAT0019871), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4741" is known as a hairpin-like precursor, "hsa-mir-4741" (miRBase Accession No. MI0017379, sequence number 390).
[0248] As used in this specification, the terms "hsa-miR-4467 gene" or "hsa-miR-4467" include the hsa-miR-4467 gene described in sequence number 134 (miRBase Accession No. MIMAT0018994), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4467" is known as a precursor, "hsa-mir-4467" (miRBase Accession No. MI0016818, sequence number 391), which takes a hairpin-like structure.
[0249] The terms "hsa-miR-4707-5p gene" or "hsa-miR-4707-5p" as used in this specification include the hsa-miR-4707-5p gene (miRBase Accession No. MIMAT0019807) described in sequence number 135, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4707-5p" is known as a precursor of "hsa-mir-4707" (miRBase Accession No. MI0017340, sequence number 392), which adopts a hairpin-like structure.
[0250] As used in this specification, the terms "hsa-miR-4271 gene" or "hsa-miR-4271" include the hsa-miR-4271 gene (miRBase Accession No. MIMAT0016901) described in sequence number 136, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Additionally, "hsa-miR-4271" is known as a hairpin-structured precursor, "hsa-mir-4271" (miRBase Accession No. MI0015879, sequence number 393).
[0251] As used in this specification, the terms "hsa-miR-4673 gene" or "hsa-miR-4673" include the hsa-miR-4673 gene described in sequence number 137 (miRBase Accession No. MIMAT0019755), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4673" is known as a precursor of "hsa-mir-4673" (miRBase Accession No. MI0017304, sequence number 394), which takes a hairpin-like structure.
[0252] The terms "hsa-miR-3184-5p gene" or "hsa-miR-3184-5p" as used in this specification include the hsa-miR-3184-5p gene (miRBase Accession No. MIMAT0015064) described in sequence number 138, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Additionally, "hsa-miR-3184-5p" is known as a precursor of "hsa-mir-3184" (miRBase Accession No. MI0014226, sequence number 395), which takes a hairpin-like structure.
[0253] As used in this specification, the terms "hsa-miR-1469 gene" or "hsa-miR-1469" include the hsa-miR-1469 gene described in sequence number 139 (miRBase Accession No. MIMAT0007347), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Kawaji H et al., 2008, BMC Genomics, Vol. 9, p. 157. Additionally, "hsa-miR-1469" is known as a hairpin-like precursor, "hsa-mir-1469" (miRBase Accession No. MI0007074, sequence number 396).
[0254] The terms "hsa-miR-4640-5p gene" or "hsa-miR-4640-5p" as used in this specification include the hsa-miR-4640-5p gene described in sequence number 140 (miRBase Accession No. MIMAT0019699), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4640-5p" is known as a precursor, "hsa-mir-4640" (miRBase Accession No. MI0017267, sequence number 397), which takes a hairpin-like structure.
[0255] As used in this specification, the terms "hsa-miR-663a gene" or "hsa-miR-663a" include the hsa-miR-663a gene described in sequence number 141 (miRBase Accession No. MIMAT0003326), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Cummins JM et al., 2006, Proc Natl Acad SciUSA, Vol. 103, pp. 3687-3692. Additionally, "hsa-miR-663a" is known as a hairpin-shaped precursor, "hsa-mir-663a" (miRBase Accession No. MI0003672, sequence number 398).
[0256] As used in this specification, the terms "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" include the hsa-miR-6791-5p gene (miRBase Accession No. MIMAT0027482) as described in sequence number 142, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6791-5p" is known as a precursor of "hsa-mir-6791" (miRBase Accession No. MI0022636, sequence number 399), which takes a hairpin-like structure.
[0257] The terms "hsa-miR-6826-5p gene" or "hsa-miR-6826-5p" as used in this specification include the hsa-miR-6826-5p gene (miRBase Accession No. MIMAT0027552) described in sequence number 143, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6826-5p" is known as a precursor of "hsa-mir-6826" (miRBase Accession No. MI0022671, sequence number 400), which takes a hairpin-like structure.
[0258] The terms "hsa-miR-4433b-3p gene" or "hsa-miR-4433b-3p" as used in this specification include the hsa-miR-4433b-3p gene (miRBase Accession No. MIMAT0030414) as described in sequence number 144, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Additionally, "hsa-miR-4433b-3p" is known as a precursor of "hsa-mir-4433b" (miRBase Accession No. MI0025511, sequence number 401), which takes a hairpin-like structure.
[0259] The terms "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" as used in this specification include the hsa-miR-1915-3p gene (miRBase Accession No. MIMAT0007892) described in sequence number 145, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Additionally, "hsa-miR-1915-3p" is known as a precursor of "hsa-mir-1915" (miRBase Accession No. MI0008336, sequence number 402), which takes a hairpin-like structure.
[0260] As used in this specification, the terms "hsa-miR-4417 gene" or "hsa-miR-4417" include the hsa-miR-4417 gene described in sequence number 146 (miRBase Accession No. MIMAT0018929), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4417" is known as a precursor, "hsa-mir-4417" (miRBase Accession No. MI0016753, sequence number 403), which takes a hairpin-like structure.
[0261] As used in this specification, the terms "hsa-miR-4449 gene" or "hsa-miR-4449" include the hsa-miR-4449 gene described in sequence number 147 (miRBase Accession No. MIMAT0018968), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4449" is known as a precursor of "hsa-mir-4449" (miRBase Accession No. MI0016792, sequence number 404), which takes a hairpin-like structure.
[0262] The terms "hsa-miR-4707-3p gene" or "hsa-miR-4707-3p" as used in this specification include the hsa-miR-4707-3p gene (miRBase Accession No. MIMAT0019808) as described in sequence number 148, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4707-3p" is known as a precursor of "hsa-mir-4707" (miRBase Accession No. MI0017340, sequence number 405), which takes a hairpin-like structure.
[0263] The terms "hsa-miR-3180-3p gene" or "hsa-miR-3180-3p" as used in this specification include the hsa-miR-3180-3p gene described in sequence number 149 (miRBase Accession No. MIMAT0015058), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Creighton CJ et al., 2010, PLoSOne, Vol. 5, e9637. Furthermore, "hsa-miR-3180-3p" is known as a precursor in hairpin-like structures: "hsa-mir-3180-1, hsa-mir-3180-2, hsa-mir-3180-3" (miRBase Accession Nos. MI0014214, MI0014215, MI0014217, sequence numbers 406, 407, 408).
[0264] The terms "hsa-miR-5585-3p gene" or "hsa-miR-5585-3p" as used in this specification include the hsa-miR-5585-3p gene (miRBase Accession No. MIMAT0022286) described in sequence number 150, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Friedlander MR et al., 2012, Nucleic Acids Res, Vol. 40, pp. 37-52. Additionally, "hsa-miR-5585-3p" is known as a precursor of "hsa-mir-5585" (miRBase Accession No. MI0019142, sequence number 409), which takes a hairpin-like structure.
[0265] As used in this specification, the terms "hsa-miR-1268a gene" or "hsa-miR-1268a" include the hsa-miR-1268a gene described in sequence number 151 (miRBase Accession No. MIMAT0005922), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. Additionally, "hsa-miR-1268a" is known as a precursor, "hsa-mir-1268a" (miRBase Accession No. MI0006405, sequence number 410), which takes a hairpin-like structure.
[0266] As used in this specification, the terms "hsa-miR-8072 gene" or "hsa-miR-8072" include the hsa-miR-8072 gene described in sequence number 152 (miRBase Accession No. MIMAT0030999), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. Additionally, "hsa-miR-8072" is known as a precursor, "hsa-mir-8072" (miRBase Accession No. MI0025908, sequence number 411), which takes a hairpin-like structure.
[0267] The terms "hsa-miR-296-5p gene" or "hsa-miR-296-5p" as used in this specification include the hsa-miR-296-5p gene described in sequence number 153 (miRBase Accession No. MIMAT0000690), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Houbavy HB et al., 2003, Dev Cell, Vol. 5, pp. 351-358. Additionally, "hsa-miR-296-5p" is known as a precursor, "hsa-mir-296" (miRBase Accession No. MI0000747, sequence number 412), which takes a hairpin-like structure.
[0268] The terms "hsa-miR-204-3p gene" or "hsa-miR-204-3p" as used in this specification include the hsa-miR-204-3p gene described in sequence number 154 (miRBase Accession No. MIMAT0022693), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Lim LP et al., 2003, Science, Vol. 299, p. 1540. Additionally, "hsa-miR-204-3p" is known as a precursor of "hsa-mir-204" (miRBase Accession No. MI0000284, sequence number 413), which takes a hairpin-like structure.
[0269] As used in this specification, the terms "hsa-miR-4454 gene" or "hsa-miR-4454" include the hsa-miR-4454 gene described in sequence number 155 (miRBase Accession No. MIMAT0018976), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4454" is known as a precursor, "hsa-mir-4454" (miRBase Accession No. MI0016800, sequence number 414), which takes a hairpin-like structure.
[0270] The terms "hsa-miR-6722-3p gene" or "hsa-miR-6722-3p" as used in this specification include the hsa-miR-6722-3p gene (miRBase Accession No. MIMAT0025854) described in sequence number 156, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Additionally, "hsa-miR-6722-3p" is known as a precursor of "hsa-mir-6722" (miRBase Accession No. MI0022557, sequence number 415), which takes a hairpin-like structure.
[0271] As used in this specification, the terms "hsa-miR-1290 gene" or "hsa-miR-1290" include the hsa-miR-1290 gene described in sequence number 157 (miRBase Accession No. MIMAT0005880), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. Additionally, "hsa-miR-1290" is known as a precursor, "hsa-mir-1290" (miRBase Accession No. MI0006352, sequence number 416), which takes a hairpin-like structure.
[0272] The terms "hsa-miR-3622a-5p gene" or "hsa-miR-3622a-5p" as used in this specification include the hsa-miR-3622a-5p gene (miRBase Accession No. MIMAT0018003) described in sequence number 158, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Witten D et al., 2010, BMCBiol, Vol. 8, p58. Additionally, "hsa-miR-3622a-5p" is known as a precursor of "hsa-mir-3622a" (miRBase Accession No. MI0016013, sequence number 417), which takes a hairpin-like structure.
[0273] The terms "hsa-miR-939-5p gene" or "hsa-miR-939-5p" as used in this specification include the hsa-miR-939-5p gene (miRBase Accession No. MIMAT0004982) described in sequence number 159, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Lui WO et al., 2007, Cancer Res, Vol. 67, pp. 6031-6043. Additionally, "hsa-miR-939-5p" is known as a precursor of "hsa-mir-939" (miRBase Accession No. MI0005761, sequence number 418), which has a hairpin-like structure.
[0274] The terms "hsa-miR-675-5p gene" or "hsa-miR-675-5p" as used in this specification include the hsa-miR-675-5p gene (miRBase Accession No. MIMAT0004284) as described in sequence number 160, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Cai X et al., 2007, RNA, Vol. 13, pp. 313-316. Additionally, "hsa-miR-675-5p" is known as a precursor of "hsa-mir-675" (miRBase Accession No. MI0005416, sequence number 419), which takes a hairpin-like structure.
[0275] As used in this specification, the terms "hsa-miR-3131 gene" or "hsa-miR-3131" include the hsa-miR-3131 gene described in sequence number 161 (miRBase Accession No. MIMAT0014996), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Additionally, "hsa-miR-3131" is known as a precursor, "hsa-mir-3131" (miRBase Accession No. MI0014151, sequence number 420), which takes a hairpin-like structure.
[0276] As used in this specification, the terms "hsa-miR-4648 gene" or "hsa-miR-4648" include the hsa-miR-4648 gene described in sequence number 162 (miRBase Accession No. MIMAT0019710), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4648" is known as a hairpin-like precursor, "hsa-mir-4648" (miRBase Accession No. MI0017275, sequence number 421).
[0277] As used in this specification, the terms "hsa-miR-1268b gene" or "hsa-miR-1268b" include the hsa-miR-1268b gene described in sequence number 163 (miRBase Accession No. MIMAT0018925), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-1268b" is known as a precursor, "hsa-mir-1268b" (miRBase Accession No. MI0016748, sequence number 422), which takes a hairpin-like structure.
[0278] The terms "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" as used in this specification include the hsa-miR-6741-5p gene (miRBase Accession No. MIMAT0027383) described in sequence number 164, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6741-5p" is known as a precursor of "hsa-mir-6741" (miRBase Accession No. MI0022586, sequence number 423), which takes a hairpin-like structure.
[0279] The terms "hsa-miR-6893-5p gene" or "hsa-miR-6893-5p" as used in this specification include the hsa-miR-6893-5p gene (miRBase Accession No. MIMAT0027686) as described in sequence number 165, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6893-5p" is known as a precursor of "hsa-mir-6893" (miRBase Accession No. MI0022740, sequence number 424), which takes a hairpin-like structure.
[0280] The terms "hsa-miR-3162-5p gene" or "hsa-miR-3162-5p" as used in this specification include the hsa-miR-3162-5p gene described in sequence number 166 (miRBase Accession No. MIMAT0015036), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Stark MS et al., 2010, PLoS One, Volume 5, e9685. Additionally, "hsa-miR-3162-5p" is known as a precursor of "hsa-mir-3162" (miRBase Accession No. MI0014192, sequence number 425), which takes a hairpin-like structure.
[0281] The terms "hsa-miR-642b-3p gene" or "hsa-miR-642b-3p" as used in this specification include the hsa-miR-642b-3p gene (miRBase Accession No. MIMAT0018444) as described in sequence number 167, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. Additionally, "hsa-miR-642b-3p" is known as a precursor of "hsa-mir-642b" (miRBase Accession No. MI0016685, sequence number 426), which has a hairpin-like structure.
[0282] As used in this specification, the terms "hsa-miR-4734 gene" or "hsa-miR-4734" include the hsa-miR-4734 gene described in sequence number 168 (miRBase Accession No. MIMAT0019859), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, as a precursor to "hsa-miR-4734," a hairpin-like structure called "hsa-mir-4734" (miRBase Accession No. MI0017371, sequence number 427) is known.
[0283] The terms "hsa-miR-150-3p gene" or "hsa-miR-150-3p" as used in this specification include the hsa-miR-150-3p gene (miRBase Accession No. MIMAT0004610) described in sequence number 169, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Lagos-Quintana M et al., 2002, CurrBiol, Vol. 12, pp. 735-739. Additionally, "hsa-miR-150-3p" is known as a precursor of "hsa-mir-150" (miRBase Accession No. MI0000479, sequence number 428), which takes a hairpin-like structure.
[0284] As used in this specification, the terms "hsa-miR-8089 gene" or "hsa-miR-8089" include the hsa-miR-8089 gene described in sequence number 170 (miRBase Accession No. MIMAT0031016), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. Additionally, "hsa-miR-8089" is known as a precursor, "hsa-mir-8089" (miRBase Accession No. MI0025925, sequence number 429), which takes a hairpin-like structure.
[0285] The terms "hsa-miR-6805-3p gene" or "hsa-miR-6805-3p" as used in this specification include the hsa-miR-6805-3p gene (miRBase Accession No. MIMAT0027511) described in sequence number 171, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6805-3p" is known as a precursor of "hsa-mir-6805" (miRBase Accession No. MI0022650, sequence number 430), which takes a hairpin-like structure.
[0286] The terms "hsa-miR-7113-3p gene" or "hsa-miR-7113-3p" as used in this specification include the hsa-miR-7113-3p gene (miRBase Accession No. MIMAT0028124) described in sequence number 172, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-7113-3p" is known as a precursor of "hsa-mir-7113" (miRBase Accession No. MI0022964, sequence number 431), which takes a hairpin-like structure.
[0287] The terms "hsa-miR-6850-5p gene" or "hsa-miR-6850-5p" as used in this specification include the hsa-miR-6850-5p gene (miRBase Accession No. MIMAT0027600) described in sequence number 173, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6850-5p" is known as a precursor of "hsa-mir-6850" (miRBase Accession No. MI0022696, sequence number 432), which takes a hairpin-like structure.
[0288] The terms "hsa-miR-6799-5p gene" or "hsa-miR-6799-5p" as used in this specification include the hsa-miR-6799-5p gene (miRBase Accession No. MIMAT0027498) described in sequence number 174, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6799-5p" is known as a hairpin-like precursor, "hsa-mir-6799" (miRBase Accession No. MI0022644, sequence number 433).
[0289] The terms "hsa-miR-6768-5p gene" or "hsa-miR-6768-5p" as used in this specification include the hsa-miR-6768-5p gene (miRBase Accession No. MIMAT0027436) described in sequence number 175, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6768-5p" is known as a precursor of "hsa-mir-6768" (miRBase Accession No. MI0022613, sequence number 434), which takes a hairpin-like structure.
[0290] The terms "hsa-miR-92b-5p gene" or "hsa-miR-92b-5p" as used in this specification include the hsa-miR-92b-5p gene described in sequence number 176 (miRBase Accession No. MIMAT0004792), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Additionally, "hsa-miR-92b-5p" is known as a hairpin-shaped precursor, "hsa-mir-92b" (miRBase Accession No. MI0003560, sequence number 435).
[0291] The terms "hsa-miR-3679-5p gene" or "hsa-miR-3679-5p" as used in this specification include the hsa-miR-3679-5p gene (miRBase Accession No. MIMAT0018104) described in sequence number 177, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Creighton CJ et al., 2010, PLoSOne, Vol. 5, e9637. Additionally, "hsa-miR-3679-5p" is known as a precursor of "hsa-mir-3679" (miRBase Accession No. MI0016080, sequence number 436), which takes a hairpin-like structure.
[0292] As used in this specification, the terms "hsa-miR-4792 gene" or "hsa-miR-4792" include the hsa-miR-4792 gene described in sequence number 178 (miRBase Accession No. MIMAT0019964), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4792" is known as a precursor, "hsa-mir-4792" (miRBase Accession No. MI0017439, sequence number 437), which takes a hairpin-like structure.
[0293] As used in this specification, the terms "hsa-miR-3656 gene" or "hsa-miR-3656" include the hsa-miR-3656 gene (miRBase Accession No. MIMAT0018076) described in sequence number 179, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, pp. 6234-6246. Additionally, "hsa-miR-3656" is known as a precursor, "hsa-mir-3656" (miRBase Accession No. MI0016056, sequence number 438), which takes a hairpin-like structure.
[0294] The terms "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" as used in this specification include the hsa-miR-92a-2-5p gene (miRBase Accession No. MIMAT0004508) described in sequence number 180, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Mourelatos Z et al., 2002, Genes Dev, Vol. 16, pp. 720-728. Additionally, "hsa-miR-92a-2-5p" is known as a hairpin-structured precursor, "hsa-mir-92a-2" (miRBase Accession No. MI0000094, sequence number 439).
[0295] As used in this specification, the terms "hsa-miR-4466 gene" or "hsa-miR-4466" include the hsa-miR-4466 gene described in sequence number 181 (miRBase Accession No. MIMAT0018993), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4466" is known as a precursor, "hsa-mir-4466" (miRBase Accession No. MI0016817, sequence number 440), which takes a hairpin-like structure.
[0296] As used in this specification, the terms "hsa-miR-4513 gene" or "hsa-miR-4513" include the hsa-miR-4513 gene described in sequence number 182 (miRBase Accession No. MIMAT0019050), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4513" is known as a precursor, "hsa-mir-4513" (miRBase Accession No. MI0016879, sequence number 441), which takes a hairpin-like structure.
[0297] The terms "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" as used in this specification include the hsa-miR-6781-5p gene (miRBase Accession No. MIMAT0027462) described in sequence number 183, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6781-5p" is known as a precursor of "hsa-mir-6781" (miRBase Accession No. MI0022626, sequence number 442), which takes a hairpin-like structure.
[0298] The terms "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" as used in this specification include the hsa-miR-4649-5p gene (miRBase Accession No. MIMAT0019711) as described in sequence number 184, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4649-5p" is known as a hairpin-like precursor, "hsa-mir-4649" (miRBase Accession No. MI0017276, sequence number 443).
[0299] The terms "hsa-miR-6775-5p gene" or "hsa-miR-6775-5p" as used in this specification include the hsa-miR-6775-5p gene (miRBase Accession No. MIMAT0027450) as described in sequence number 185, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6775-5p" is known as a hairpin-like precursor of "hsa-mir-6775" (miRBase Accession No. MI0022620, sequence number 444).
[0300] As used in this specification, the terms "hsa-miR-4651 gene" or "hsa-miR-4651" include the hsa-miR-4651 gene described in sequence number 186 (miRBase Accession No. MIMAT0019715), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4651" is known as a precursor, "hsa-mir-4651" (miRBase Accession No. MI0017279, sequence number 445), which takes a hairpin-like structure.
[0301] As used in this specification, the terms "hsa-miR-3195 gene" or "hsa-miR-3195" include the hsa-miR-3195 gene described in sequence number 187 (miRBase Accession No. MIMAT0015079), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Additionally, "hsa-miR-3195" is known as a precursor, "hsa-mir-3195" (miRBase Accession No. MI0014240, sequence number 446), which takes a hairpin-like structure.
[0302] The terms "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" as used in this specification include the hsa-miR-6726-5p gene (miRBase Accession No. MIMAT0027353) as described in sequence number 188, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6726-5p" is known as a precursor of "hsa-mir-6726" (miRBase Accession No. MI0022571, sequence number 447), which takes a hairpin-like structure.
[0303] The terms "hsa-miR-6872-3p gene" or "hsa-miR-6872-3p" as used in this specification include the hsa-miR-6872-3p gene (miRBase Accession No. MIMAT0027645) as described in sequence number 189, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6872-3p" is known as a precursor of "hsa-mir-6872" (miRBase Accession No. MI0022719, sequence number 448), which takes a hairpin-like structure.
[0304] The terms "hsa-miR-371a-5p gene" or "hsa-miR-371a-5p" as used in this specification include the hsa-miR-371a-5p gene (miRBase Accession No. MIMAT0004687) as described in sequence number 190, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Suh MR et al., 2004, Dev Biol, Vol. 270, pp. 488-498. Additionally, "hsa-miR-371a-5p" is known as a hairpin-like precursor, "hsa-mir-371a" (miRBase Accession No. MI0000779, sequence number 449).
[0305] The terms "hsa-miR-6777-5p gene" or "hsa-miR-6777-5p" as used in this specification include the hsa-miR-6777-5p gene (miRBase Accession No. MIMAT0027454) as described in sequence number 191, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6777-5p" is known as a hairpin-like precursor, "hsa-mir-6777" (miRBase Accession No. MI0022622, sequence number 450).
[0306] The terms "hsa-miR-6789-5p gene" or "hsa-miR-6789-5p" as used in this specification include the hsa-miR-6789-5p gene (miRBase Accession No. MIMAT0027478) as described in sequence number 192, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6789-5p" is known as a precursor of "hsa-mir-6789" (miRBase Accession No. MI0022634, sequence number 451), which takes a hairpin-like structure.
[0307] As used in this specification, the terms "hsa-miR-7975 gene" or "hsa-miR-7975" include the hsa-miR-7975 gene (miRBase Accession No. MIMAT0031178) as described in sequence number 193, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Velthut-Meikas A et al., 2013, Mol Endocrinol, Vol. 27, pp. 1128-1141. Additionally, "hsa-miR-7975" is known as a precursor of "hsa-mir-7975" (miRBase Accession No. MI0025751, sequence number 452), which takes a hairpin-like structure.
[0308] The terms "hsa-miR-6821-5p gene" or "hsa-miR-6821-5p" as used in this specification include the hsa-miR-6821-5p gene (miRBase Accession No. MIMAT0027542) described in sequence number 194, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6821-5p" is known as a precursor of "hsa-mir-6821" (miRBase Accession No. MI0022666, sequence number 453), which takes a hairpin-like structure.
[0309] As used in this specification, the terms "hsa-miR-4534 gene" or "hsa-miR-4534" include the hsa-miR-4534 gene described in sequence number 195 (miRBase Accession No. MIMAT0019073), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4534" is known as a precursor of "hsa-mir-4534" (miRBase Accession No. MI0016901, sequence number 454), which takes a hairpin-like structure.
[0310] The terms "hsa-miR-619-5p gene" or "hsa-miR-619-5p" as used in this specification include the hsa-miR-619-5p gene (miRBase Accession No. MIMAT0026622) as described in sequence number 196, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Additionally, "hsa-miR-619-5p" is known as a hairpin-shaped precursor, "hsa-mir-619" (miRBase Accession No. MI0003633, sequence number 455).
[0311] The terms "hsa-miR-7107-5p gene" or "hsa-miR-7107-5p" as used in this specification include the hsa-miR-7107-5p gene (miRBase Accession No. MIMAT0028111) as described in sequence number 197, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-7107-5p" is known as a precursor of "hsa-mir-7107" (miRBase Accession No. MI0022958, sequence number 456), which takes a hairpin-like structure.
[0312] The terms "hsa-miR-1228-3p gene" or "hsa-miR-1228-3p" as used in this specification include the hsa-miR-1228-3p gene (miRBase Accession No. MIMAT0005583) as described in sequence number 198, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Berezikov E et al., 2007, MolCell, Vol. 28, pp. 328-336. Additionally, "hsa-miR-1228-3p" is known as a precursor of "hsa-mir-1228" (miRBase Accession No. MI0006318, sequence number 457), which takes a hairpin-like structure.
[0313] The terms "hsa-miR-6774-5p gene" or "hsa-miR-6774-5p" as used in this specification include the hsa-miR-6774-5p gene (miRBase Accession No. MIMAT0027448) as described in sequence number 199, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6774-5p" is known as a precursor of "hsa-mir-6774" (miRBase Accession No. MI0022619, sequence number 458), which takes a hairpin-like structure.
[0314] The terms "hsa-miR-6805-5p gene" or "hsa-miR-6805-5p" as used in this specification include the hsa-miR-6805-5p gene described in sequence number 200 (miRBase Accession No. MIMAT0027510), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6805-5p" is known as a precursor of "hsa-mir-6805" (miRBase Accession No. MI0022650, sequence number 459), which takes a hairpin-like structure.
[0315] The terms "hsa-miR-23a-3p gene" or "hsa-miR-23a-3p" as used in this specification include the hsa-miR-23a-3p gene (miRBase Accession No. MIMAT0000078) as described in sequence number 201, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Lagos-Quintana M et al., 2001, Science, Vol. 294, pp. 853-858. Additionally, "hsa-miR-23a-3p" is known as a hairpin-shaped precursor, "hsa-mir-23a" (miRBase Accession No. MI0000079, sequence number 460).
[0316] The terms "hsa-miR-4665-5p gene" or "hsa-miR-4665-5p" as used in this specification include the hsa-miR-4665-5p gene (miRBase Accession No. MIMAT0019739) as described in sequence number 202, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4665-5p" is known as a hairpin-like precursor, "hsa-mir-4665" (miRBase Accession No. MI0017295, sequence number 461).
[0317] As used in this specification, the terms "hsa-miR-4505 gene" or "hsa-miR-4505" include the hsa-miR-4505 gene described in sequence number 203 (miRBase Accession No. MIMAT0019041), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4505" is known as a precursor, "hsa-mir-4505" (miRBase Accession No. MI0016868, sequence number 462), which takes a hairpin-like structure.
[0318] The terms "hsa-miR-4638-5p gene" or "hsa-miR-4638-5p" as used in this specification include the hsa-miR-4638-5p gene described in sequence number 204 (miRBase Accession No. MIMAT0019695), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4638-5p" is known as a hairpin-like precursor, "hsa-mir-4638" (miRBase Accession No. MI0017265, sequence number 463).
[0319] As used in this specification, the terms "hsa-miR-24-3p gene" or "hsa-miR-24-3p" include the hsa-miR-24-3p gene described in sequence number 205 (miRBase Accession No. MIMAT0000080), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Lagos-Quintana M et al., 2001, Science, Vol. 294, pp. 853-858. Additionally, "hsa-miR-24-3p" is known as a precursor in hairpin-like structures, namely "hsa-mir-24-1" and "hsa-mir-24-2" (miRBase Accession Nos. MI0000080, MI0000081, sequence numbers 464 and 465).
[0320] As used in this specification, the terms "hsa-miR-3135b gene" or "hsa-miR-3135b" include the hsa-miR-3135b gene described in sequence number 206 (miRBase Accession No. MIMAT0018985), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-3135b" is known as a precursor of "hsa-mir-3135b" (miRBase Accession No. MI0016809, sequence number 466), which takes a hairpin-like structure.
[0321] The terms "hsa-miR-4745-5p gene" or "hsa-miR-4745-5p" as used in this specification include the hsa-miR-4745-5p gene (miRBase Accession No. MIMAT0019878) as described in sequence number 207, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4745-5p" is known as a precursor of "hsa-mir-4745" (miRBase Accession No. MI0017384, sequence number 467), which takes a hairpin-like structure.
[0322] The terms "hsa-miR-128-1-5p gene" or "hsa-miR-128-1-5p" as used in this specification include the hsa-miR-128-1-5p gene (miRBase Accession No. MIMAT0026477) described in sequence number 208, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Additionally, "hsa-miR-128-1-5p" is known as a hairpin-like precursor, "hsa-mir-128-1" (miRBase Accession No. MI0000447, sequence number 468).
[0323] As used in this specification, the terms "hsa-miR-4476 gene" or "hsa-miR-4476" include the hsa-miR-4476 gene described in sequence number 209 (miRBase Accession No. MIMAT0019003), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4476" is known as a precursor, "hsa-mir-4476" (miRBase Accession No. MI0016828, sequence number 469), which takes a hairpin-like structure.
[0324] The terms "hsa-miR-4687-3p gene" or "hsa-miR-4687-3p" as used in this specification include the hsa-miR-4687-3p gene (miRBase Accession No. MIMAT0019775) described in sequence number 210, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4687-3p" is known as a hairpin-like precursor of "hsa-mir-4687" (miRBase Accession No. MI0017319, sequence number 470).
[0325] As used in this specification, the terms "hsa-miR-3665 gene" or "hsa-miR-3665" include the hsa-miR-3665 gene (miRBase Accession No. MIMAT0018087) as described in sequence number 211, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Xie X et al., 2005, Nature, Vol. 434, pp. 338-345. Additionally, "hsa-miR-3665" is known as a precursor of "hsa-mir-3665" (miRBase Accession No. MI0016066, sequence number 471), which adopts a hairpin-like structure.
[0326] The terms "hsa-miR-6806-5p gene" or "hsa-miR-6806-5p" as used in this specification include the hsa-miR-6806-5p gene (miRBase Accession No. MIMAT0027512) as described in sequence number 212, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6806-5p" is known as a precursor of "hsa-mir-6806" (miRBase Accession No. MI0022651, sequence number 472), which takes a hairpin-like structure.
[0327] As used in this specification, the terms "hsa-miR-3937 gene" or "hsa-miR-3937" include the hsa-miR-3937 gene (miRBase Accession No. MIMAT0018352) described in sequence number 213, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Additionally, "hsa-miR-3937" is known as a precursor, "hsa-mir-3937" (miRBase Accession No. MI0016593, sequence number 473), which takes a hairpin-like structure.
[0328] As used in this specification, the terms "hsa-miR-711 gene" or "hsa-miR-711" include the hsa-miR-711 gene described in sequence number 214 (miRBase Accession No. MIMAT0012734), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p39. Additionally, "hsa-miR-711" is known as a hairpin-like precursor, "hsa-mir-711" (miRBase Accession No. MI0012488, sequence number 474).
[0329] As used in this specification, the terms "hsa-miR-3141 gene" or "hsa-miR-3141" include the hsa-miR-3141 gene described in sequence number 215 (miRBase Accession No. MIMAT0015010), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Additionally, "hsa-miR-3141" is known as a hairpin-like precursor, "hsa-mir-3141" (miRBase Accession No. MI0014165, sequence number 475).
[0330] As used in this specification, the terms "hsa-miR-3188 gene" or "hsa-miR-3188" include the hsa-miR-3188 gene described in sequence number 216 (miRBase Accession No. MIMAT0015070), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Additionally, "hsa-miR-3188" is known as a precursor, "hsa-mir-3188" (miRBase Accession No. MI0014232, sequence number 476), which takes a hairpin-like structure.
[0331] As used in this specification, the terms "hsa-miR-4281 gene" or "hsa-miR-4281" include the hsa-miR-4281 gene described in sequence number 217 (miRBase Accession No. MIMAT0016907), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Additionally, "hsa-miR-4281" is known as a precursor, "hsa-mir-4281" (miRBase Accession No. MI0015885, sequence number 477), which takes a hairpin-like structure.
[0332] As used in this specification, the terms "hsa-miR-5196-5p gene" or "hsa-miR-5196-5p" include the hsa-miR-5196-5p gene (miRBase Accession No. MIMAT0021128) as described in sequence number 218, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Schotte D et al., 2011, Leukemia, Vol. 25, pp. 1389-1399. Additionally, "hsa-miR-5196-5p" is known as a precursor of "hsa-mir-5196" (miRBase Accession No. MI0018175, sequence number 478), which takes a hairpin-like structure.
[0333] The terms "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" as used in this specification include the hsa-miR-6880-5p gene (miRBase Accession No. MIMAT0027660) described in sequence number 219, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6880-5p" is known as a precursor, "hsa-mir-6880" (miRBase Accession No. MI0022727, sequence number 479), which takes a hairpin-like structure.
[0334] As used in this specification, the terms "hsa-miR-3960 gene" or "hsa-miR-3960" include the hsa-miR-3960 gene described in sequence number 220 (miRBase Accession No. MIMAT0019337), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Hu R et al., 2011, J Biol Chem, Vol. 286, pp. 12328-12339. Additionally, "hsa-miR-3960" is known as a precursor, and a hairpin-like structure, "hsa-mir-3960" (miRBase Accession No. MI0016964, sequence number 480), is also known.
[0335] As used in this specification, the terms "hsa-miR-3648 gene" or "hsa-miR-3648" include the hsa-miR-3648 gene described in sequence number 221 (miRBase Accession No. MIMAT0018068), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, pp. 6234-6246. Additionally, "hsa-miR-3648" is known as a precursor, and its hairpin-like structures are known as "hsa-mir-3648-1, hsa-mir-3648-2" (miRBase Accession Nos. MI0016048, MI0031512, sequence numbers 481, 482).
[0336] The terms "hsa-miR-6721-5p gene" or "hsa-miR-6721-5p" as used in this specification include the hsa-miR-6721-5p gene described in sequence number 222 (miRBase Accession No. MIMAT0025852), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Additionally, "hsa-miR-6721-5p" is known as a precursor of "hsa-mir-6721" (miRBase Accession No. MI0022556, sequence number 483), which takes a hairpin-like structure.
[0337] As used in this specification, the terms "hsa-miR-4492 gene" or "hsa-miR-4492" include the hsa-miR-4492 gene described in sequence number 223 (miRBase Accession No. MIMAT0019027), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4492" is known as a precursor of "hsa-mir-4492" (miRBase Accession No. MI0016854, sequence number 484), which takes a hairpin-like structure.
[0338] The terms "hsa-miR-744-5p gene" or "hsa-miR-744-5p" as used in this specification include the hsa-miR-744-5p gene described in sequence number 224 (miRBase Accession No. MIMAT0004945), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Additionally, "hsa-miR-744-5p" is known as a hairpin-like precursor, "hsa-mir-744" (miRBase Accession No. MI0005559, sequence number 485).
[0339] As used in this specification, the terms "hsa-miR-7704 gene" or "hsa-miR-7704" include the hsa-miR-7704 gene described in sequence number 225 (miRBase Accession No. MIMAT0030019), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Swaminathan S et al., 2013, Biochem Biophys Res Commun., Vol. 434, pp. 228-234. Additionally, "hsa-miR-7704" is known as a precursor, "hsa-mir-7704" (miRBase Accession No. MI0025240, sequence number 486), which takes a hairpin-like structure.
[0340] The terms "hsa-miR-4749-5p gene" or "hsa-miR-4749-5p" as used in this specification include the hsa-miR-4749-5p gene (miRBase Accession No. MIMAT0019885) described in sequence number 226, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Persson H et al., 2011, CancerRes, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4749-5p" is known as a hairpin-like precursor, "hsa-mir-4749" (miRBase Accession No. MI0017388, sequence number 487).
[0341] The terms "hsa-miR-6794-5p gene" or "hsa-miR-6794-5p" as used in this specification include the hsa-miR-6794-5p gene (miRBase Accession No. MIMAT0027488) as described in sequence number 227, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6794-5p" is known as a precursor of "hsa-mir-6794" (miRBase Accession No. MI0022639, sequence number 488), which takes a hairpin-like structure.
[0342] As used in this specification, the terms "hsa-miR-6511a-5p gene" or "hsa-miR-6511a-5p" include the hsa-miR-6511a-5p gene (miRBase Accession No. MIMAT0025478) as described in sequence number 228, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Joyce CE et al., 2011, Hum MolGenet, Vol. 20, pp. 4025-4040. In addition, "hsa-miR-6511a-5p" is known as a precursor, and "hsa-mir-6511a-1, hsa-mir-6511a-2, hsa-mir-6511a-3, hsa-mir-6511a-4" with hairpin-like structures are known (miRBase Accession No. MI0022223, MI0023564, MI0023565, MI0023566, serial numbers 489, 490, 491, 492).
[0343] The terms "hsa-miR-6824-5p gene" or "hsa-miR-6824-5p" as used in this specification include the hsa-miR-6824-5p gene described in sequence number 229 (miRBase Accession No. MIMAT0027548), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6824-5p" is known as a precursor of "hsa-mir-6824" (miRBase Accession No. MI0022669, sequence number 493), which takes a hairpin-like structure.
[0344] As used in this specification, the terms "hsa-miR-762 gene" or "hsa-miR-762" include the hsa-miR-762 gene described in sequence number 230 (miRBase Accession No. MIMAT0010313), as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Additionally, "hsa-miR-762" is known as a hairpin-like precursor, "hsa-mir-762" (miRBase Accession No. MI0003892, sequence number 494).
[0345] The terms "hsa-miR-6836-3p gene" or "hsa-miR-6836-3p" as used in this specification include the hsa-miR-6836-3p gene (miRBase Accession No. MIMAT0027575) as described in sequence number 231, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6836-3p" is known as a precursor of "hsa-mir-6836" (miRBase Accession No. MI0022682, sequence number 495), which takes a hairpin-like structure.
[0346] The terms "hsa-miR-6727-5p gene" or "hsa-miR-6727-5p" as used in this specification include the hsa-miR-6727-5p gene described in sequence number 232 (miRBase Accession No. MIMAT0027355), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6727-5p" is known as a hairpin-like precursor, "hsa-mir-6727" (miRBase Accession No. MI0022572, sequence number 496).
[0347] As used in this specification, the terms "hsa-miR-4739 gene" or "hsa-miR-4739" include the hsa-miR-4739 gene described in sequence number 233 (miRBase Accession No. MIMAT0019868), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4739" is known as a hairpin-like precursor, "hsa-mir-4739" (miRBase Accession No. MI0017377, sequence number 497).
[0348] As used in this specification, the terms "hsa-miR-7977 gene" or "hsa-miR-7977" include the hsa-miR-7977 gene described in sequence number 234 (miRBase Accession No. MIMAT0031180), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Velthut-Meikas A et al., 2013, Mol Endocrinol, Vol. 27, pp. 1128-1141. Additionally, "hsa-miR-7977" is known as a hairpin-like precursor, "hsa-mir-7977" (miRBase Accession No. MI0025753, sequence number 498).
[0349] As used in this specification, the terms "hsa-miR-4484 gene" or "hsa-miR-4484" include the hsa-miR-4484 gene described in sequence number 235 (miRBase Accession No. MIMAT0019018), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4484" is known as a precursor of "hsa-mir-4484" (miRBase Accession No. MI0016845, sequence number 499), which takes a hairpin-like structure.
[0350] The terms "hsa-miR-6515-3p gene" or "hsa-miR-6515-3p" as used in this specification include the hsa-miR-6515-3p gene (miRBase Accession No. MIMAT0025487) as described in sequence number 236, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Joyce CE et al., 2011, Hum MolGenet, Vol. 20, pp. 4025-4040. Additionally, "hsa-miR-6515-3p" is known as a precursor of "hsa-mir-6515" (miRBase Accession No. MI0022227, sequence number 500), which takes a hairpin-like structure.
[0351] The terms "hsa-miR-373-5p gene" or "hsa-miR-373-5p" as used in this specification include the hsa-miR-373-5p gene (miRBase Accession No. MIMAT0000725) described in sequence number 237, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Suh MR et al., 2004, Dev Biol, Vol. 270, pp. 488-498. Additionally, "hsa-miR-373-5p" is known as a hairpin-like precursor, "hsa-mir-373" (miRBase Accession No. MI0000781, sequence number 501).
[0352] As used in this specification, the terms "hsa-miR-4258 gene" or "hsa-miR-4258" include the hsa-miR-4258 gene described in sequence number 238 (miRBase Accession No. MIMAT0016879), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Additionally, "hsa-miR-4258" is known as a hairpin-like precursor, "hsa-mir-4258" (miRBase Accession No. MI0015857, sequence number 502).
[0353] As used in this specification, the terms "hsa-miR-4674 gene" or "hsa-miR-4674" include the hsa-miR-4674 gene described in sequence number 239 (miRBase Accession No. MIMAT0019756), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4674" is known as a hairpin-like precursor, "hsa-mir-4674" (miRBase Accession No. MI0017305, sequence number 503).
[0354] As used in this specification, the terms "hsa-miR-3180 gene" or "hsa-miR-3180" include the hsa-miR-3180 gene described in sequence number 240 (miRBase Accession No. MIMAT0018178), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Additionally, "hsa-miR-3180" is known as a precursor, and its precursors are known to take hairpin-like structures as "hsa-mir-3180-4, hsa-mir-3180-5" (miRBase Accession Nos. MI0016408, MI0016409, sequence numbers 504, 505).
[0355] As used in this specification, the terms "hsa-miR-6076 gene" or "hsa-miR-6076" include the hsa-miR-6076 gene described in sequence number 241 (miRBase Accession No. MIMAT0023701), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Voellenkle C et al., 2012, RNA, Vol. 18, pp. 472-484. Additionally, "hsa-miR-6076" is known as a precursor, "hsa-mir-6076" (miRBase Accession No. MI0020353, sequence number 506), which takes a hairpin-like structure.
[0356] The terms "hsa-miR-1238-5p gene" or "hsa-miR-1238-5p" as used in this specification include the hsa-miR-1238-5p gene described in sequence number 242 (miRBase Accession No. MIMAT0022947), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Berezikov E et al., 2007, MolCell, Vol. 28, pp. 328-336. Additionally, "hsa-miR-1238-5p" is known as a precursor of "hsa-mir-1238" (miRBase Accession No. MI0006328, sequence number 507), which takes a hairpin-like structure.
[0357] As used in this specification, the terms "hsa-miR-4463 gene" or "hsa-miR-4463" include the hsa-miR-4463 gene described in sequence number 243 (miRBase Accession No. MIMAT0018987), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4463" is known as a precursor, "hsa-mir-4463" (miRBase Accession No. MI0016811, sequence number 508), which takes a hairpin-like structure.
[0358] As used in this specification, the terms "hsa-miR-4486 gene" or "hsa-miR-4486" include the hsa-miR-4486 gene described in sequence number 244 (miRBase Accession No. MIMAT0019020), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Additionally, "hsa-miR-4486" is known as a precursor, "hsa-mir-4486" (miRBase Accession No. MI0016847, sequence number 509), which takes a hairpin-like structure.
[0359] As used in this specification, the terms "hsa-miR-4730 gene" or "hsa-miR-4730" include the hsa-miR-4730 gene described in sequence number 245 (miRBase Accession No. MIMAT0019852), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4730" is known as a precursor of "hsa-mir-4730" (miRBase Accession No. MI0017367, sequence number 510), which takes a hairpin-like structure.
[0360] The terms "hsa-miR-6766-3p gene" or "hsa-miR-6766-3p" as used in this specification include the hsa-miR-6766-3p gene (miRBase Accession No. MIMAT0027433) as described in sequence number 246, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6766-3p" is known as a hairpin-like precursor, "hsa-mir-6766" (miRBase Accession No. MI0022611, sequence number 511).
[0361] As used in this specification, the terms "hsa-miR-4286 gene" or "hsa-miR-4286" include the hsa-miR-4286 gene described in sequence number 247 (miRBase Accession No. MIMAT0016916), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Additionally, "hsa-miR-4286" is known as a precursor, "hsa-mir-4286" (miRBase Accession No. MI0015894, sequence number 512), which takes a hairpin-like structure.
[0362] As used in this specification, the terms "hsa-miR-6511a-5p gene" or "hsa-miR-6511a-5p" include the hsa-miR-6511a-5p gene (miRBase Accession No. MIMAT0025478) as described in sequence number 248, as well as other species homologs or orthologs of this gene. The gene can be obtained using the methods described in Joyce CE et al., 2011, Hum MolGenet, Vol. 20, pp. 4025-4040. In addition, "hsa-miR-6511a-5p" is known as a precursor, and "hsa-mir-6511a-1, hsa-mir-6511a-2, hsa-mir-6511a-3, hsa-mir-6511a-4" with hairpin-like structures are known (miRBase Accession No. MI0022223, MI0023564, MI0023565, MI0023566, serial numbers 513, 514, 515, 516).
[0363] As used in this specification, the terms "hsa-miR-4739 gene" or "hsa-miR-4739" include the hsa-miR-4739 gene described in sequence number 249 (miRBase Accession No. MIMAT0019868), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Additionally, "hsa-miR-4739" is known as a hairpin-like precursor, "hsa-mir-4739" (miRBase Accession No. MI0017377, sequence number 517).
[0364] The terms "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" as used in this specification include the hsa-miR-6749-5p gene described in sequence number 250 (miRBase Accession No. MIMAT0027398), other species homologs or orthologs of this gene, etc. The gene can be obtained using the methods described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Additionally, "hsa-miR-6749-5p" is known as a precursor of "hsa-mir-6749" (miRBase Accession No. MI0022594, sequence number 518), which takes a hairpin-like structure.
[0365] Furthermore, when mature miRNAs are excised from hairpin-like RNA precursors as mature miRNAs, they are sometimes excised one to several bases shorter or longer than the sequence, and / or undergo base substitutions to become mutants, known as isomiR (Morin RD. et al., 2008, Genome Res., Vol. 18, pp. 610-621). In miRBase version 20, in addition to the base sequences shown in any of the sequences 1-250, a large number of mutants and fragments of the base sequences shown in any of the sequences 519-812, known as isomiR, are also shown. These mutants can also be obtained as miRNAs with the base sequences shown in any of the sequences 1-250. That is, the serial numbers 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, 8 of the present invention 8, 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, 1 57, 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 The longest mutant of a polynucleotide consisting of the base sequences shown in 216, 217, 218, 220, 221, 222, 223, 224, 226, 228, 233, 235, 236, 237, 239, 240, 243, 244, 245, 247, 248, and 249, or a polynucleotide sequence in which u is t, is, for example, registered in miRBase version 20.The following serial numbers can be listed: 519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 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, 66 5, 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, 7 The polynucleotides shown are 41, 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. Additionally,The serial numbers of this invention are 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, and 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, 15 7, 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 The following are examples of mutants of polynucleotides consisting of the base sequences shown in 216, 217, 218, 220, 221, 222, 223, 224, 226, 228, 233, 235, 236, 237, 239, 240, 243, 244, 245, 247, 248, and 249, or sequences of such sequences where u is t, as, for example, the shortest mutants registered in miRBase version 20.The following serial numbers can be listed: 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 The sequences shown are polynucleotides: 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. In addition to these mutants and fragments,The following sequence numbers can also be listed as registered in miRBase: 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, 2 Polynucleotides containing isomiR at sequences 04, 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. Furthermore, as examples of polynucleotides containing the base sequences shown in any of sequences 1 to 250, polynucleotides shown in any of sequences 251 to 518 as precursors can be listed.
[0366] The names of the genes indicated by sequence numbers 1 to 812 and their miRBase Accession Nos are shown in Table 1.
[0367] In this specification, "can specifically bind" means that the nucleic acid probes or primers used in this invention can bind to a specific target nucleic acid and do not substantially bind to other nucleic acids.
[0368] Table 1
[0369]
[0370]
[0371]
[0372]
[0373]
[0374]
[0375]
[0376]
[0377]
[0378]
[0379]
[0380]
[0381]
[0382]
[0383]
[0384]
[0385]
[0386]
[0387]
[0388]
[0389] This specification contains the disclosure of Japanese Patent Application No. 2016-073132 (filed on March 31, 2016), which forms the basis of the priority of this application.
[0390] The effects of the invention
[0391] According to the present invention, early pancreatic cancer or precancerous lesions of pancreatic cancer can be detected easily and with high accuracy.
[0392] For example, by measuring the expression levels of several miRNAs in the blood, serum, and / or plasma of patients that can be collected in a low-invasive manner, it is easy to detect whether a patient has early-stage pancreatic cancer or precancerous lesions of pancreatic cancer. Attached Figure Description
[0393] Figure 1This shows the relationship between the base sequences of hsa-miR-1343-3p (as shown in sequence number 118) and hsa-miR-1343-5p (as shown in sequence number 14), generated from hsa-miR-1343 (as shown in sequence number 264) which is a precursor.
[0394] Figure 2 The left figure shows the expression levels of hsa-miR-6784-5p (accession number 1) in patients with precancerous pancreatic lesions (21 patients), early-stage pancreatic cancer patients (31 patients), and healthy individuals (123 patients) selected as the training cohort. A discriminant expression (3.10 × hsa-miR - miR-6784-5p - 39.85) was generated using Fisher discriminant analysis, with the discriminant score obtained from this expression as the ordinate and the cohort as the abscissa. The dashed line in the figure represents the discriminant boundary used to distinguish between the two groups, where the discriminant score is 0. Figure 2 The right figure shows the expression levels of hsa-miR-6784-5p (serial number 1) in patients with precancerous pancreatic lesions (12 patients), early-stage pancreatic cancer patients (13 patients), and healthy individuals (61 patients) selected as the validation cohort. The graph is plotted with the discrimination score obtained by the discriminant formula derived from the learning cohort as the vertical axis and the cohort as the horizontal axis. The dashed line in the figure represents the discrimination boundary used to distinguish between the two groups when the discrimination score is 0.
[0395] Figure 3 The left figure shows the expression levels of hsa-miR-6784-5p (accession number 1) and hsa-miR-1181 (accession number 2) in patients with precancerous pancreatic lesions (21 patients), early pancreatic cancer patients (31 patients), and healthy individuals (123 individuals) selected as the learning sample groups. A discriminant formula (1.90 × hsa-miR-6784-5p + 1.72 × hsa-miR-1181 - 34.50) was generated using Fisher discriminant analysis. The discriminant score obtained from this formula is plotted on the ordinate, and the sample groups are plotted on the abscissa. The dashed line in the figure represents the discriminant boundary used to distinguish between the two groups, where the discriminant score is 0. Figure 3 The right figure shows the expression levels of hsa-miR-6784-5p (accession number 1) and hsa-miR-1181 (accession number 2) in patients with precancerous pancreatic lesions (12 patients), early pancreatic cancer patients (13 patients), and healthy individuals (61 patients) selected as the validation sample group. The graph is plotted with the discrimination score obtained by the discriminant formula constructed from the learning sample group as the vertical axis and the sample group as the horizontal axis. The dashed line in the figure represents the discrimination boundary used to distinguish between the two groups when the discrimination score is 0.
[0396] Figure 4The above figure shows the results of a study sample group consisting of 21 patients with precancerous pancreatic lesions, 31 patients with early-stage pancreatic cancer, 128 healthy individuals, 61 patients with advanced pancreatic cancer, 66 patients with cholangiocarcinoma, 51 patients with breast cancer, 35 patients with prostate cancer, 31 patients with colorectal cancer, 32 patients with gastric cancer, 34 patients with esophageal cancer, 38 patients with liver cancer, 15 patients with benign pancreatic diseases, and 26 patients with benign prostatic diseases. The sample groups included hsa-miR-4695-5p (serial number 106), hsa-miR-5090 (serial number 12), and hsa-miR-4673 (serial number 137). The expression levels of sa-miR-6813-5p (accession number 119) and hsa-miR-642a-3p (accession number 105) were determined using Fisher discriminant analysis to generate a discriminant formula (0.48×hsa-miR-4695-5p-1.75×hsa-miR-5090+1.31×hsa-miR-4673-0.98×hsa-miR-6813-5p-1.16×hsa-miR-642a-3p+15.39). A graph was plotted with the discriminant score obtained from this formula on the ordinate and the sample groups on the abscissa. The dashed line in the graph represents the discriminant boundary used to distinguish between two groups, where the discriminant score is 0. Figure 4 The figure below shows the expression levels of hsa-miR-4695-5p (serial number 106), hsa-miR-5090 (serial number 12), hsa-miR-4673 (serial number 137), hsa-miR-6813-5p (serial number 119), and hsa-miR-642a-3p (serial number 105) in 12 patients with precancerous pancreatic lesions, 13 patients with early-stage pancreatic cancer, 56 healthy individuals, 39 patients with advanced pancreatic cancer, 32 patients with cholangiocarcinoma, 23 patients with breast cancer, 17 patients with prostate cancer, 19 patients with colorectal cancer, 18 patients with gastric cancer, 16 patients with esophageal cancer, 14 patients with liver cancer, and 24 patients with benign pancreatic and prostate diseases, selected as the validation sample group. The dashed line in the figure represents the discrimination boundary used to distinguish between two groups when the discrimination score is 0. Detailed Implementation
[0397] The present invention will now be described in more detail.
[0398] 1. Target nucleic acids for early pancreatic cancer or precancerous lesions of pancreatic cancer
[0399] As a nucleic acid probe or primer used for detecting early pancreatic cancer or precancerous lesions using the above-defined method of the present invention, the primary target nucleic acid for detecting early pancreatic cancer or precancerous lesions, or markers of the presence and / or absence of early pancreatic cancer or precancerous lesion cells, comprises nucleic acids selected from 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-6769 a-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, hs a-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, h sa-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, h sa-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,At least one miRNA from the group consisting of 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.
[0400] other early pancreatic cancer or precancerous pancreatic cancer lesions that can be further combined with these miRNAs, that is, selected from the group consisting of 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-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-6893-5 p, 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, h sa-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-3141hsa-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, hs At least one miRNA from the group consisting of a-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 be preferred as the target nucleic acid.
[0401] Among the above-mentioned miRNAs, for example, human genes comprising the nucleotide sequence represented by any one of SEQ ID NOs: 1 to 250 (that is, 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-6803-5p, 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-61 25, 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-m iR-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-mi R-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-286 1、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、hs a-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-5phsa-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-146 9, 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, hs a-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-m iR-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-7107-5phsa-miR-1228-3p, hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p, hsa-miR-4665-5p, hsa-miR-4505, hsa-mi R-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-m iR-5196-5p, hsa-miR-6880-5p, hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p, hsa-miR-4492, hsa-miR-744-5p, hs a-miR-7704, hsa-miR-4749-5p, hsa-miR-6794-5p, hsa-miR-6511a-5p, hsa-miR-6824-5p, hsa-miR-762, hsa-miR-683 6-3p, hsa-miR-6727-5p, hsa-miR-4739, hsa-miR-7977, hsa-miR-4484, hsa-miR-6515-3p, hsa-miR-373-5p, hsa-miR- Genes, their homologs, their transcripts, and / or their mutants or derivatives are defined as follows: 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, their homologs, their transcripts, and / or their mutants or derivatives. Genes, homologs, transcripts, mutants, and derivatives are as defined above.
[0402] The preferred target nucleic acid is a human gene containing the base sequence shown in any one of the sequence numbers 1 to 812, its transcript, more preferably the transcript, i.e., miRNA, pri-miRNA or pre-miRNA as the precursor RNA of the transcript.
[0403] The primary target genes are the hsa-miR-6784-5p gene, their homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0404] The second target gene is the hsa-miR-1181 gene, its homologs, its transcripts, or its mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0405] The third target gene is the hsa-miR-671-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0406] The fourth target gene is the hsa-miR-6857-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0407] The fifth target gene is the hsa-miR-4276 gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0408] The sixth target gene is the hsa-miR-1914-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0409] The seventh target gene is the hsa-miR-149-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0410] The eighth target gene is the hsa-miR-937-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0411] The ninth target gene is the hsa-miR-4675 gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0412] The 10th target gene is the hsa-miR-6795-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0413] The 11th target gene is the hsa-miR-4731-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0414] The 12th target gene is the hsa-miR-5090 gene, its homologs, its transcripts, or its mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and could serve as markers for early pancreatic cancer or precancerous lesions.
[0415] The 13th target gene is the hsa-miR-3620-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0416] The 14th target gene is the hsa-miR-1343-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0417] The 15th target gene is the hsa-miR-6717-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts that are currently unknown and could serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0418] The 16th target gene is the hsa-miR-6825-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions of the pancreas.
[0419] The 17th target gene is the hsa-miR-6738-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and could serve as markers for early pancreatic cancer or precancerous lesions.
[0420] The 18th target gene is the hsa-miR-6769a-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0421] The 19th target gene is the hsa-miR-4728-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0422] The 20th target gene is the hsa-miR-652-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0423] The 21st target gene is the hsa-miR-4257 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and could serve as markers for early pancreatic cancer or precancerous lesions.
[0424] The 22nd target gene is the hsa-miR-6785-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0425] The 23rd target gene is the hsa-miR-7110-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0426] The 24th target gene is the hsa-miR-6887-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0427] The 25th target gene is the hsa-miR-887-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0428] The 26th target gene is the hsa-miR-1228-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0429] The 27th target gene is the hsa-miR-5572 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0430] The 28th target gene is the hsa-miR-6782-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0431] The 29th target gene is the hsa-miR-4298 gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0432] The 30th target gene is the hsa-miR-6786-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0433] The 31st target gene is the hsa-miR-5010-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of pancreatic cancer.
[0434] The 32nd target gene is the hsa-miR-6087 gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0435] The 33rd target gene is the hsa-miR-6765-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0436] The 34th target gene is the hsa-miR-6732-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0437] The 35th target gene is the hsa-miR-6787-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0438] The 36th target gene is the hsa-miR-6737-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0439] The 37th target gene is the hsa-miR-128-2-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and could serve as markers for early pancreatic cancer or precancerous lesions.
[0440] The 38th target gene is the hsa-miR-4270 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0441] The 39th target gene is the hsa-miR-6861-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0442] The 40th target gene is the hsa-miR-6756-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0443] The 41st target gene is the hsa-miR-1229-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and could serve as markers for early pancreatic cancer or precancerous lesions.
[0444] The 42nd target gene is the hsa-miR-6891-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0445] The 43rd target gene is the hsa-miR-6848-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0446] The 44th target gene is the hsa-miR-1237-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0447] The 45th target gene is the hsa-miR-30c-1-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and could serve as markers for early pancreatic cancer or precancerous lesions.
[0448] The 46th target gene is the hsa-miR-1233-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0449] The 47th target gene is the hsa-miR-211-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0450] The 48th target gene is the hsa-miR-4758-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0451] The 49th target gene is the hsa-miR-614 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0452] The 50th target gene is the hsa-miR-6746-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0453] The 51st target gene is the hsa-miR-1915-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts that are unknown and could serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0454] The 52nd target gene is the hsa-miR-4688 gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0455] The 53rd target gene is the hsa-miR-3917 gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions of the pancreas.
[0456] The 54th target gene is the hsa-miR-5787 gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0457] The 55th target gene is the hsa-miR-4632-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts that are unknown and could serve as biomarkers for early pancreatic cancer or precancerous lesions.
[0458] The 56th target gene is the hsa-miR-6126 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0459] The 57th target gene is the hsa-miR-135a-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0460] The 58th target gene is the hsa-miR-8063 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and could serve as markers for early pancreatic cancer or precancerous lesions.
[0461] The 59th target gene is the hsa-miR-5698 gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts that are unknown and could serve as markers for early pancreatic cancer or precancerous lesions.
[0462] The 60th target gene is the hsa-miR-6089 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0463] The 61st target gene is the hsa-miR-498 gene, its homologs, its transcripts, or its mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0464] The 62nd target gene is the hsa-miR-296-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0465] The 63rd target gene is the hsa-miR-4419b gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0466] The 64th target gene is the hsa-miR-6802-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0467] The 65th target gene is the hsa-miR-6829-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0468] The 66th target gene is the hsa-miR-6803-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0469] The 67th target gene is the hsa-miR-1199-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0470] The 68th target gene is the hsa-miR-6840-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0471] The 69th target gene is the hsa-miR-6752-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0472] The 70th target gene is the hsa-miR-6798-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0473] The 71st target gene is the hsa-miR-6131 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0474] The 72nd target gene is the hsa-miR-4667-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts that are currently unknown and could serve as biomarkers for early pancreatic cancer or precancerous lesions of the pancreas.
[0475] The 73rd target gene is the hsa-miR-6510-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0476] The 74th target gene is the hsa-miR-4690-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0477] The 75th target gene is the hsa-miR-920 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0478] The 76th target gene is the hsa-miR-23b-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0479] The 77th target gene is the hsa-miR-4448 gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0480] The 78th target gene is the hsa-miR-2110 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0481] The 79th target gene is the hsa-miR-4706 gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0482] The 80th target gene is the hsa-miR-7845-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions.
[0483] The 81st target gene is the hsa-miR-6808-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are reports of changes in the expression of genes or their transcripts that are currently unknown and can serve as markers for early pancreatic cancer or precancerous lesions of the pancreas.
[0484] The 82nd target gene is the hsa-miR-4447 gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0485] The 83rd target gene is the hsa-miR-6869-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of changes in the expression of unknown genes or their transcripts serving as biomarkers for early pancreatic cancer or precancerous lesions.
[0486] The 84th target gene is the hsa-miR-1908-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0487] The 85th target gene is the hsa-miR-6729-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0488] The 86th target gene is the hsa-miR-5195-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0489] The 87th target gene is the hsa-miR-638 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0490] The 88th target gene is the hsa-miR-6125 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0491] The 89th target gene is the hsa-miR-3178 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0492] The 90th target gene is the hsa-miR-3196 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0493] The 91st target gene is the hsa-miR-8069 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0494] The 92nd target gene is the hsa-miR-4723-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0495] The 93rd target gene is the hsa-miR-4746-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0496] The 94th target gene is the hsa-miR-4689 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0497] The 95th target gene is the hsa-miR-6816-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0498] The 96th target gene is the hsa-miR-6757-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0499] The 97th target gene is the hsa-miR-7109-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0500] The 98th target gene is the hsa-miR-6724-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0501] The 99th target gene is the hsa-miR-1225-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0502] The 100th target gene is the hsa-miR-6875-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0503] The 101st target gene is the hsa-miR-7108-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0504] The 102nd target gene is the hsa-miR-4508 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0505] The 103rd target gene is the hsa-miR-6085 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0506] The 104th target gene is the hsa-miR-6779-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0507] The 105th target gene is the hsa-miR-642a-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0508] The 106th target gene is the hsa-miR-4695-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0509] The 107th target gene is the hsa-miR-7847-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0510] The 108th target gene is the hsa-miR-3197 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0511] The 109th target gene is the hsa-miR-6769b-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0512] The 110th target gene is the hsa-miR-7641 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0513] The 111th target gene is the hsa-miR-187-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0514] The 112th target gene is the hsa-miR-3185 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0515] The 113th target gene is the hsa-miR-2861 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0516] The 114th target gene is the hsa-miR-3940-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0517] The 115th target gene is the hsa-miR-1203 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0518] The 116th target gene is the hsa-miR-615-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0519] The 117th target gene is the hsa-miR-4787-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0520] The 118th target gene is the hsa-miR-1343-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0521] The 119th target gene is the hsa-miR-6813-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0522] The 120th target gene is the hsa-miR-1225-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0523] The 121st target gene is the hsa-miR-602 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0524] The 122nd target gene is the hsa-miR-4488 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0525] The target gene 123 is the hsa-miR-125a-3p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0526] The 124th target gene is the hsa-miR-5100 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0527] The 125th target gene is the hsa-miR-4294 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0528] The 126th target gene is the hsa-miR-1231 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0529] The 127th target gene is the hsa-miR-6765-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0530] The 128th target gene is the hsa-miR-4442 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0531] The 129th target gene is the hsa-miR-718 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0532] The 130th target gene is the hsa-miR-6780b-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0533] The 131st target gene is the hsa-miR-6090 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0534] The 132nd target gene is the hsa-miR-6845-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0535] The 133rd target gene is the hsa-miR-4741 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0536] The 134th target gene is the hsa-miR-4467 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0537] The 135th target gene is the hsa-miR-4707-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0538] The 136th target gene is the hsa-miR-4271 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0539] The 137th target gene is the hsa-miR-4673 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0540] The 138th target gene is the hsa-miR-3184-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0541] The 139th target gene is the hsa-miR-1469 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0542] The 140th target gene is the hsa-miR-4640-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0543] The 141st target gene is the hsa-miR-663a gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0544] The 142nd target gene is the hsa-miR-6791-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0545] The 143rd target gene is the hsa-miR-6826-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0546] The 144th target gene is the hsa-miR-4433b-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0547] The 145th target gene is the hsa-miR-1915-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0548] The 146th target gene is the hsa-miR-4417 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0549] The 147th target gene is the hsa-miR-4449 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0550] The 148th target gene is the hsa-miR-4707-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0551] The 149th target gene is the hsa-miR-3180-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0552] The 150th target gene is the hsa-miR-5585-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0553] The 151st target gene is the hsa-miR-1268a gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as markers for early pancreatic cancer or precancerous lesions of pancreatic cancer (see Patent Document 4 above).
[0554] The 152nd target gene is the hsa-miR-8072 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0555] The 153rd target gene is the hsa-miR-296-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as markers for early pancreatic cancer or precancerous lesions of pancreatic cancer (see Patent Document 5 above).
[0556] The 154th target gene is the hsa-miR-204-3p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0557] The 155th target gene is the hsa-miR-4454 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0558] The 156th target gene is the hsa-miR-6722-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0559] The 157th target gene is the hsa-miR-1290 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0560] The 158th target gene is the hsa-miR-3622a-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0561] The 159th target gene is the hsa-miR-939-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as markers for early pancreatic cancer or precancerous lesions of pancreatic cancer (see Patent Document 4 above).
[0562] The 160th target gene is the hsa-miR-675-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0563] The 161st target gene is the hsa-miR-3131 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0564] The 162nd target gene is the hsa-miR-4648 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0565] The 163rd target gene is the hsa-miR-1268b gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0566] The 164th target gene is the hsa-miR-6741-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0567] The 165th target gene is the hsa-miR-6893-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0568] The 166th target gene is the hsa-miR-3162-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0569] The 167th target gene is the hsa-miR-642b-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as markers for early pancreatic cancer or precancerous lesions of pancreatic cancer (see Patent Document 4 above).
[0570] The 168th target gene is the hsa-miR-4734 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0571] The 169th target gene is the hsa-miR-150-3p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0572] The 170th target gene is the hsa-miR-8089 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0573] The 171st target gene is the hsa-miR-6805-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0574] The 172nd target gene is the hsa-miR-7113-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0575] The 173rd target gene is the hsa-miR-6850-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0576] The 174th target gene is the hsa-miR-6799-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0577] The 175th target gene is the hsa-miR-6768-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0578] The 176th target gene is the hsa-miR-92b-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0579] The 177th target gene is the hsa-miR-3679-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0580] The 178th target gene is the hsa-miR-4792 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0581] The 179th target gene is the hsa-miR-3656 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0582] The 180th target gene is the hsa-miR-92a-2-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0583] The 181st target gene is the hsa-miR-4466 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0584] The 182nd target gene is the hsa-miR-4513 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0585] The 183rd target gene is the hsa-miR-6781-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0586] The 184th target gene is the hsa-miR-4649-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0587] The 185th target gene is the hsa-miR-6775-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0588] The 186th target gene is the hsa-miR-4651 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0589] The 187th target gene is the hsa-miR-3195 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0590] The 188th target gene is the hsa-miR-6726-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0591] The 189th target gene is the hsa-miR-6872-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0592] The 190th target gene is the hsa-miR-371a-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0593] The 191st target gene is the hsa-miR-6777-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0594] The 192nd target gene is the hsa-miR-6789-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0595] The 193rd target gene is the hsa-miR-7975 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0596] The 194th target gene is the hsa-miR-6821-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0597] The 195th target gene is the hsa-miR-4534 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0598] The 196th target gene is the hsa-miR-619-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0599] The 197th target gene is the hsa-miR-7107-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0600] The 198th target gene is the hsa-miR-1228-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0601] The 199th target gene is the hsa-miR-6774-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0602] The 200th target gene is the hsa-miR-6805-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0603] The 201st target gene is the hsa-miR-23a-3p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 3 above).
[0604] The 202nd target gene is the hsa-miR-4665-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0605] The 203rd target gene is the hsa-miR-4505 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0606] The 204th target gene is the hsa-miR-4638-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0607] The 205th target gene is the hsa-miR-24-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0608] The 206th target gene is the hsa-miR-3135b gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0609] The 207th target gene is the hsa-miR-4745-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0610] The 208th target gene is the hsa-miR-128-1-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0611] The 209th target gene is the hsa-miR-4476 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0612] The 210th target gene is the hsa-miR-4687-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0613] The 211th target gene is the hsa-miR-3665 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0614] The 212th target gene is the hsa-miR-6806-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0615] The 213th target gene is the hsa-miR-3937 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0616] The 214th target gene is the hsa-miR-711 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0617] The 215th target gene is the hsa-miR-3141 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0618] The 216th target gene is the hsa-miR-3188 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0619] The 217th target gene is the hsa-miR-4281 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0620] The 218th target gene is the hsa-miR-5196-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0621] The 219th target gene is the hsa-miR-6880-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0622] The 220th target gene is the hsa-miR-3960 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0623] The 221st target gene is the hsa-miR-3648 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 1 above).
[0624] The target gene 222 is the hsa-miR-6721-5p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0625] The 223rd target gene is the hsa-miR-4492 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0626] The 224th target gene is the hsa-miR-744-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0627] The 225th target gene is the hsa-miR-7704 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0628] The 226th target gene is the hsa-miR-4749-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0629] The 227th target gene is the hsa-miR-6794-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for pancreatic cancer.
[0630] The 228th target gene is the hsa-miR-6511a-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for pancreatic cancer.
[0631] The 229th target gene is the hsa-miR-6824-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for pancreatic cancer.
[0632] The 230th target gene is the hsa-miR-762 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0633] The target gene 231 is the hsa-miR-6836-3p gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0634] The 232nd target gene is the hsa-miR-6727-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0635] The 233rd target gene is the hsa-miR-4739 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0636] The 234th target gene is the hsa-miR-7977 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0637] The 235th target gene is the hsa-miR-4484 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0638] The 236th target gene is the hsa-miR-6515-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0639] The 237th target gene is the hsa-miR-373-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0640] The 238th target gene is the hsa-miR-4258 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0641] The 239th target gene is the hsa-miR-4674 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0642] The 240th target gene is the hsa-miR-3180 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0643] The 241st target gene is the hsa-miR-6076 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0644] The 242nd target gene is the hsa-miR-1238-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0645] The 243rd target gene is the hsa-miR-4463 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0646] The 244th target gene is the hsa-miR-4486 gene, its homologs, its transcripts, or its mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0647] The 245th target gene is the hsa-miR-4730 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0648] The 246th target gene is the hsa-miR-6766-3p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for pancreatic cancer.
[0649] The 247th target gene is the hsa-miR-4286 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Patent Document 2 above).
[0650] The 248th target gene is the hsa-miR-6511a-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for pancreatic cancer.
[0651] The 249th target gene is the hsa-miR-4739 gene, its homologs, their transcripts, or their mutants or derivatives. There are currently reports that changes in the expression of genes or their transcripts can serve as biomarkers for pancreatic cancer (see Non-Patent Literature 5 above).
[0652] The 250th target gene is the hsa-miR-6749-5p gene, its homologs, their transcripts, or their mutants or derivatives. There are no reports to date of altered expression of genes or their transcripts serving as biomarkers for pancreatic cancer.
[0653] 2. Nucleic acid probes or primers for detecting early pancreatic cancer or precancerous lesions of the pancreas.
[0654] In this invention, nucleic acids that can specifically bind to the target nucleic acids described above as markers of early pancreatic cancer or precancerous pancreatic lesions can be used as nucleic acids, such as nucleic acid probes or primers, for detecting or diagnosing early pancreatic cancer or precancerous pancreatic lesions.
[0655] In this invention, nucleic acid probes or primers capable of detecting or diagnosing early pancreatic cancer or precancerous lesions of pancreatic cancer are provided. These probes or primers can qualitatively and / or quantitatively determine the target nucleic acids for early pancreatic cancer or precancerous lesions derived from humans, including 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, and hsa-miR-4731-5p. 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-472 8-5p, 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, h sa-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-6803-5p, 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 a combination thereof, and optionally 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, which can be combined with the foregoinghsa-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-46 73, 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-1915-3 p, 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-mi R-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-m iR-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-m iR-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-3195hsa-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, h sa-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-mi The presence, expression level, or quantity of R-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, their homologs, their transcripts, or their mutants or derivatives.
[0656] Compared to healthy individuals, the expression levels of the aforementioned target nucleic acids in subjects with early pancreatic cancer or precancerous lesions of pancreatic cancer vary, with some showing an increase and others a decrease (hereinafter referred to as "increase / decrease"). For example, Table 2 illustrates the changes in the expression levels of target miRNAs corresponding to sequence numbers 1 to 226 in the blood (serum) of patients (humans) with precancerous lesions of pancreatic cancer, relative to healthy individuals. As shown in Table 2, depending on the type of target miRNA, there are miRNAs with increased expression and conversely, miRNAs with decreased expression. In this invention, any of the target miRNAs selected and described in the specification can be used in subjects for the detection and assessment of early pancreatic cancer or precancerous lesions of pancreatic cancer.
[0657] Therefore, according to the present invention, by measuring the expression levels of the aforementioned target nucleic acid in bodily fluids derived from subjects suspected of having early pancreatic cancer or precancerous lesions of pancreatic cancer (e.g., humans) and bodily fluids derived from healthy individuals, and comparing these samples, it is possible to effectively and accurately detect early pancreatic cancer or precancerous lesions of pancreatic cancer. Furthermore, according to the present invention, by measuring the expression levels of the aforementioned target nucleic acid in bodily fluids derived from subjects suspected of having early pancreatic cancer or precancerous lesions of pancreatic cancer (e.g., humans), and bodily fluids derived from patients with advanced pancreatic cancer, bile duct cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, liver cancer, benign pancreatic diseases, benign prostatic diseases, or combinations thereof, and comparing these samples, it is possible to effectively and specifically and accurately identify early pancreatic cancer or precancerous lesions of pancreatic cancer from other cancers, benign diseases, etc.
[0658] The nucleic acid probes or primers that can be used in this invention are nucleic acid probes that can specifically bind to polynucleotides composed of at least one, at least two, at least three, at least four, or at least five base sequences shown in sequence numbers 1-83, 227-229, 246, 248, and 250, or primers used to amplify polynucleotides composed of at least one, at least two, at least three, at least four, or at least five base sequences shown in sequence numbers 1-83, 227-229, 246, 248, and 250.
[0659] The nucleic acid probes or primers that can be used in this invention may further comprise nucleic acid probes that specifically bind to polynucleotides composed of at least one, at least two, at least three, at least four, or at least five base sequences shown in sequence numbers 84–226, 230–245, 247, and 249, or primers for amplifying polynucleotides composed of at least one, at least two, at least three, at least four, or at least five base sequences shown in sequence numbers 84–226, 230–245, 247, and 249.
[0660] Specifically, the aforementioned nucleic acid probes or primers comprise: a polynucleotide set and its complementary polynucleotide set selected from the base sequences shown in any one of the sequence numbers 1 to 250, or the base sequences in which u is t; a polynucleotide set and its complementary polynucleotide set that hybridize separately to DNA composed of base sequences complementary to the aforementioned base sequences under stringent conditions (described later); and a combination of one or more polynucleotides from a polynucleotide set containing 15 or more, preferably 17 or more, consecutive bases from the base sequences of these polynucleotide sets. Relatedly, the target miRNA used in this invention also comprises, for example, precursor miRNAs as shown in sequence numbers 251 to 518 in Table 1, and miRNA isoforms (isomiRNAs) as shown in sequence numbers 519 to 812. miRNA isoforms include short miRNA isoforms with approximately 15 bases, long miRNA isoforms with approximately 29 bases, and miRNA isoforms with mutations such as substitutions. Therefore, in this invention, the aforementioned nucleic acid probes or primers also include nucleic acid probes or primers capable of measuring the expression of precursor miRNAs and target miRNA isoforms. These polynucleotides can be used as nucleic acid probes and primers for detecting target nucleic acids, namely the aforementioned markers of early pancreatic cancer or precancerous pancreatic lesions.
[0661] More specifically, examples of nucleic acid probes or primers that can be used in this invention are at least one (i.e., one or more) polynucleotides selected from the group consisting of any of the following polynucleotides (a) to (e).
[0662] (a) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 1–83, 227–229, 246, 248, and 250, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.
[0663] (b) A polynucleotide containing the base sequence shown in any of the sequence numbers 1–83, 227–229, 246, 248, and 250.
[0664] (c) A polynucleotide, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, consisting of a base sequence complementary to the base sequence represented by any of the sequence numbers 1–83, 227–229, 246, 248, and 250, or a base sequence in which u is t.
[0665] (d) A polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequence numbers 1–83, 227–229, 246, 248, and 250, or a base sequence in which u is t, and,
[0666] (e) A polynucleotide that hybridizes with any of the polynucleotides (a) to (d) above under strict conditions.
[0667] In addition to at least one (i.e., one or more) polynucleotides selected from any of the above-described polynucleotides (a) to (e), the nucleic acid probes or primers that can be used in this invention may also contain at least one (i.e., one or more) polynucleotides as shown in any of the following (f) to (j).
[0668] (f) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 84–226, 230–245, 247, and 249, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.
[0669] (g) A polynucleotide containing the base sequence shown in any of the sequence numbers 84–226, 230–245, 247, and 249.
[0670] (h) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 84–226, 230–245, 247, and 249, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.
[0671] (i) a polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequences 84–226, 230–245, 247, and 249, or a base sequence in which u is t, and,
[0672] (j) A polynucleotide that hybridizes with any of the polynucleotides (f) to (i) above under strict conditions.
[0673] In the aforementioned polynucleotides, "the fragment containing 15 or more consecutive bases of the polynucleotide" can include, for example, a range of bases from 15 consecutive bases to less than the total number of bases in the sequence, from 17 bases to less than the total number of bases in the sequence, from 19 bases to less than the total number of bases in the sequence, but is not limited to these ranges.
[0674] The polynucleotides or their fragments used in this invention can be either DNA or RNA.
[0675] The polynucleotides used in this invention can be produced using general techniques such as DNA recombination technology, PCR, and methods using an automated DNA / RNA synthesizer.
[0676] DNA recombination technology and PCR can use techniques described in, for example, Ausubel et al., Current Protocols in Molecular Biology, John Willey & Sons, US (1993); Samb...
Claims
1. The use of nucleic acids that can specifically bind to the polynucleotide hsa-miR-1343-5p, a marker of early pancreatic cancer or precancerous lesions of pancreatic cancer, for the manufacture of a kit for the detection of early pancreatic cancer or precancerous lesions of pancreatic cancer.
2. According to claim 1, the nucleic acid is a polynucleotide selected from the group consisting of polynucleotides shown in any one of (a) to (e) below. (a) A polynucleotide consisting of the base sequence shown in sequence number 14 or a sequence of bases in which u is t, or a fragment of the polynucleotide containing 15 or more consecutive bases. (b) A polynucleotide containing the base sequence shown in sequence number 14. (c) A polynucleotide consisting of a base sequence complementary to the base sequence shown in sequence number 14 or a base sequence in which u is t, or a fragment of the polynucleotide containing 15 or more consecutive bases. (d) A polynucleotide containing a base sequence complementary to the base sequence shown in sequence number 14 or a base sequence in which u is t, and (e) A polynucleotide that hybridizes with any of the polynucleotides (a) to (d) above under strict conditions.
3. According to claim 1, the kit further comprises a nucleic acid capable of specifically binding to other early pancreatic cancer or precancerous lesion markers, said other early pancreatic cancer or precancerous lesion markers being selected from 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-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-42 98. 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-30 c-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-6803-5p, 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-47 06, 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-6749-5p, 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-mi R-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-1 225-3p, 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-5100hsa-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-6781-5 p, 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-6777-5pAt least one polynucleotide selected from the group consisting of 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-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.、 4. In accordance with the use described in claim 3, the nucleic acid capable of specifically binding to other early pancreatic cancer or precancerous lesion markers is a polynucleotide selected from the group consisting of polynucleotides shown in any one of (f) to (j) below. (f) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 1 to 13 and 15 to 250, or a base sequence in which u is t, or a fragment of the polynucleotide containing 15 or more consecutive bases. (g) A polynucleotide containing the base sequence shown in any of the sequence numbers 1–13 and 15–250. (h) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 1-13 and 15-250, or a base sequence in which u is t, or a fragment of the polynucleotide containing 15 or more consecutive bases. (i) A polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequence numbers 1–13 and 15–250, or a base sequence in which u is t. (j) A polynucleotide that hybridizes with any of the polynucleotides (f) to (i) above under strict conditions.
5. The use of nucleic acids that can specifically bind to the polynucleotide hsa-miR-1343-5p, a marker of early pancreatic cancer or precancerous lesions of pancreatic cancer, for the manufacture of devices for the detection of early pancreatic cancer or precancerous lesions of pancreatic cancer.
6. The use according to claim 5, wherein the nucleic acid is a polynucleotide selected from the group consisting of polynucleotides shown in any one of (a) to (e) below. (a) A polynucleotide consisting of the base sequence shown in sequence number 14 or a sequence of bases in which u is t, or a fragment of the polynucleotide containing 15 or more consecutive bases. (b) A polynucleotide containing the base sequence shown in sequence number 14. (c) A polynucleotide consisting of a base sequence complementary to the base sequence shown in sequence number 14 or a base sequence in which u is t, or a fragment of the polynucleotide containing 15 or more consecutive bases. (d) A polynucleotide containing a base sequence complementary to the base sequence shown in sequence number 14 or a base sequence in which u is t, and (e) A polynucleotide that hybridizes with any of the polynucleotides (a) to (d) above under strict conditions.
7. The use according to claim 5, wherein the device further comprises a nucleic acid capable of specifically binding to other early pancreatic cancer or precancerous lesion markers, said other early pancreatic cancer or precancerous lesion markers being selected from 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-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-42 98. 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-30 c-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-6803-5p, 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-47 06, 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-6749-5p, 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-mi R-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-1 225-3p, 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-5100hsa-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-6781-5 p, 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-6777-5pAt least one polynucleotide from the group consisting of 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-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.
8. In accordance with the use described in claim 7, the nucleic acid capable of specifically binding to other early pancreatic cancer or precancerous lesion markers is a polynucleotide selected from the group consisting of polynucleotides shown in any one of (f) to (j) below. (f) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 1 to 13 and 15 to 250, or a base sequence in which u is t, or a fragment of the polynucleotide containing 15 or more consecutive bases. (g) A polynucleotide containing the base sequence shown in any of the sequence numbers 1–13 and 15–250. (h) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 1-13 and 15-250, or a base sequence in which u is t, or a fragment of the polynucleotide containing 15 or more consecutive bases. (i) A polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequence numbers 1–13 and 15–250, or a base sequence in which u is t. (j) A polynucleotide that hybridizes with any of the polynucleotides (f) to (i) above under strict conditions.
9. The use according to any one of claims 5 to 8, wherein the device is a device for determination by hybridization technique.
10. The hybridization technique described in claim 9 is a nucleic acid array technique.
11. The use according to any one of claims 1 to 8, wherein the above-described kit or device is used to determine the expression level of the target in a sample of a subject, and using the measured expression level and the same measured control expression level of a healthy body, to evaluate in vitro whether the subject has early pancreatic cancer or precancerous lesions, or does not have early pancreatic cancer or precancerous lesions, thereby detecting whether early pancreatic cancer or precancerous lesions are present or absent in the subject.
12. The use according to claim 11, wherein the subject is a human being.
13. The use according to claim 11, wherein the sample is blood, serum or plasma.
14. The use according to any one of claims 1 to 8, wherein the above-described kit or device is used to determine the expression level of a detection target in a sample of a subject, and by incorporating the expression level of the detection target from the sample of the subject into the discriminant, to evaluate whether early pancreatic cancer or precancerous lesions of pancreatic cancer are present or absent. The discriminant is constructed by using the target expression levels from samples of subjects known to have early pancreatic cancer or precancerous lesions and from samples of healthy subjects as teacher samples, and is able to distinguish between early pancreatic cancer or precancerous lesions and healthy subjects.
15. The use according to claim 14, wherein the subject is a human being.
16. The use according to claim 14, wherein the sample is blood, serum or plasma.
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