Gastric cancer detection kit or device and detection method
A kit using nucleic acids that bind to specific miRNAs addresses the limitations of current gastric cancer detection methods by providing accurate, minimally invasive, and cost-effective screening for gastric cancer.
Patent Information
- Application Number
- JP2025158154
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2015-03-31
- Filing Date
- 2025-09-24
- Publication Date
- 2025-12-23
AI Technical Summary
Current gastric cancer detection methods, including imaging tests and serum protein markers, are inadequate for early detection, leading to high mortality rates and unnecessary testing or missed treatment opportunities, while miRNA-based methods lack industrial practicality and are costly for large-scale screening.
A kit using nucleic acids that specifically bind to a set of miRNAs, including miR-4257, miR-6726-5p, and others, for detecting gastric cancer from minimally invasive blood samples, providing accurate differentiation between cancer patients and healthy subjects.
The kit offers highly accurate and minimally invasive gastric cancer detection, reducing radiation exposure and costs, and improving early detection rates.
Smart Images

Figure 2025186464000058 
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Abstract
Description
[Technical Field]
[0001] The present invention relates to a kit or device for detecting gastric cancer, which is used to test whether a subject is affected with gastric cancer and which contains a nucleic acid capable of specifically binding to a specific miRNA, and a method for detecting gastric cancer, which comprises measuring the expression level of the miRNA using the nucleic acid. [Background technology]
[0002] The stomach is a pouch-like digestive organ connected to the esophagus. It temporarily stores food entering the stomach and secretes gastric juices, performing the first stage of digestion. The stomach is divided into the cardia, which is near the entrance to the esophagus; the pylorus, which is near the exit to the duodenum; and the remaining portion, the body (Non-Patent Document 1). According to statistics on cancer incidence and mortality by site in Japan published by the Center for Cancer Control and Information, National Cancer Center, a National Research and Development Agency, the number of gastric cancer patients in 2010 was estimated to be 125,730, consisting of 86,728 men and 39,002 women. Furthermore, the number of deaths from gastric cancer in 2012 was 49,129, consisting of 32,206 men and 16,923 women, making it the second leading cause of cancer death in Japan. Furthermore, in the United States, it is estimated that 22,220 people will develop gastric cancer and 10,990 will die from the disease in 2014 (Non-Patent Document 1).
[0003] The stage of gastric cancer is defined in Non-Patent Document 2 and is classified into stages 0, IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV based on tumor size, invasiveness, lymph node metastasis, distant metastasis, etc. The 5-year relative survival rate for gastric cancer is highly dependent on the stage of cancer progression, and has been reported to be 57-71% for stage I, 33-46% for stage II, 9-20% for stage III, and 4% for stage IV (Non-Patent Document 1). Therefore, because early detection of gastric cancer leads to improved survival rates, there is a strong desire to provide means to enable early detection.
[0004] Gastric cancer treatment involves a combination of surgery, chemotherapy, and radiation therapy. In particular, for very early gastric cancer with no suspicion of lymph node metastasis, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are often applicable, allowing for treatment without placing a burden on the patient.
[0005] In Japan, men and women aged 40 and over are recommended to undergo annual stomach cancer screening in order to detect stomach cancer early. Gastric X-ray examination has been shown to be effective as a method of stomach cancer screening, and if the results of the X-ray examination indicate that a more detailed examination is necessary, a gastroscopy examination is performed. In addition, imaging diagnostics such as CT, PET, and MRI are also used to detect stomach cancer (Non-Patent Document 1).
[0006] On the other hand, no blood markers for screening for gastric cancer have been established. While it has been suggested that serum protein tumor markers such as CEA and CA19-9 are associated with gastric cancer (Non-Patent Document 3), there is insufficient evidence to recommend their use for screening. Meanwhile, as shown in Patent Documents 1 to 3, although still in the research stage, there are reports that gastric cancer can be detected by measuring the expression levels of microRNA (miRNA) in biological samples such as blood, or by combining the expression levels of miRNA with the expression levels of other protein markers.
[0007] Patent Document 1 discloses a method for detecting cancer, including gastric cancer, using hsa-miR-125a-3p in the blood.
[0008] Patent Document 2 discloses a method for detecting gastric cancer using hsa-miR-23a-3p, miR-92-1, miR-92-2 (miR-92a-1-3p, miR-92a-2-3p), as well as miR-128b (miR-128-2-3p), miR-30c (miR-30c-5p), miR-135-1, miR-135-2 (miR-135a-5p), miR-149 (miR-149-5p), and other miRNAs in blood and tissues.
[0009] Patent Document 3 discloses a method for detecting stomach cancer using hsa-miR-451 and 468 (hsa-miR-468-5p) in the blood. [Prior art documents] [Patent documents]
[0010] [Patent Document 1] International Publication No. 2010 / 062706 [Patent Document 2] Japanese Patent Application Laid-Open No. 2014-060993 [Patent Document 3] Japanese Patent Application Laid-Open No. 2013-085542 [Non-patent literature]
[0011] [Non-Patent Document 1] American Cancer Society "Stomach Cancer," edited by 2013, pp. 3, 6, 18-20 http: / / www.cancer.org / acs / groups / cid / documents / webcontent / 003141-pdf.pdf [Non-patent document 2] Sobin, L. et al., “TNM Classification of Malignant Tumors 7th Edition Japanese Version” 2010, p.69-73 [Non-patent document 3] Kim, HJ et al., Acta Oncologica, 2009, Vol. 48, pp. 385-390 Summary of the Invention [Problem to be solved by the invention]
[0012] The present invention aims to discover a novel stomach cancer tumor marker and provide a method for effectively detecting stomach cancer using a nucleic acid capable of specifically binding to the marker. Primary tests for stomach cancer include imaging tests such as CT, PET, and MRI, as well as gastric X-ray examinations, which are commonly used in Japan (Non-Patent Document 1). However, stomach cancer remains the second leading cause of cancer death in Japan, and imaging tests cannot necessarily be said to be effective in preventing deaths from stomach cancer.
[0013] Tumor markers for detecting gastric cancer include, for example, CEA and CA19-9. Generally, as shown in Non-Patent Document 3, 5 ng / mL for CEA and 37 U / mL for CA19-9 are used as reference values. However, while these tumor markers can be useful for assessing gastric cancer recurrence and therapeutic efficacy, their expression is rarely elevated in early-stage gastric cancer, making them unsuitable for gastric cancer screening. Furthermore, tumor markers such as CEA and CA19-9 can be elevated for reasons other than gastric cancer, making it difficult to determine the presence or absence of gastric cancer using these markers alone. Furthermore, incorrectly diagnosing other cancers as gastric cancer can result in missed opportunities for appropriate treatment or the wrong medical treatment, placing unnecessary financial and physical burdens on patients.
[0014] Additionally, although still in the research stage, there have been reports of using the expression levels of microRNA (miRNA) in biological samples such as blood to identify stomach cancer, as described below, but none of these have yet been put into practical use.
[0015] Patent Document 1 discloses a method for detecting cancer, including gastric cancer, using hsa-miR-125a-3p and other miRNAs in blood. However, this detection method does not describe the specific accuracy, sensitivity, specificity, and other detection performance for distinguishing gastric cancer, and therefore lacks industrial practicality.
[0016] Patent Document 2 describes a method for detecting gastric cancer using hsa-miR-23a-3p, miR-92-1, miR-92-2 (miR-92a-1-3p, miR-92a-2-3p) in blood or tissue, and also using miR-128 (miR-128-2-5p), miR-30c (miR-30c-5p), miR-135-1, miR-135-2 (miR-135a-5p), miR-149 (miR-149-5p), and other miRNAs.
[0017] Among these, hsa-miR-23a-3p, miR-92-1, and miR-92-2 (miR-92a-1-3p, miR-92a-2-3p) have been described as miRNAs specifically for detecting gastric cancer. However, there is no description of verification of markers in blood, and specific detection examples are for miRNAs in tissues, which is not an easy screening test and therefore has little industrial practicality.
[0018] As such, existing tumor markers for gastric cancer detection either have poor performance or lack specific detection methods and performance for research-stage markers. Therefore, their use could result in unnecessary additional testing due to misidentification of healthy subjects as gastric cancer patients, or missed treatment opportunities due to overlooking gastric cancer patients. Furthermore, measuring miRNAs, which consist of tens to hundreds of miRNAs, increases testing costs, making them difficult to use for large-scale screening such as health checkups. Furthermore, sampling gastric tissue for tumor marker measurement is highly invasive for patients, making it undesirable. Therefore, there is a need for highly accurate gastric cancer markers that can be detected from minimally invasive blood samples and accurately distinguish between gastric cancer patients and healthy subjects. In particular, imaging tests such as gastric X-rays, currently used for early detection of gastric cancer, have issues such as radiation exposure and high costs. Therefore, providing a simpler primary gastric cancer screening test would benefit both subjects and healthcare authorities. [Means for solving the problem]
[0019] As a result of intensive research to solve the above problems, the inventors discovered several genes that can be used as markers for detecting gastric cancer from blood, which can be collected minimally invasively, and found that gastric cancer can be significantly detected by using nucleic acids that can specifically bind to these genes, thereby completing the present invention.
[0020] <Summary of the Invention> That is, the present invention has the following features. (1) miR-4257, miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR- 6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, mi R-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, m iR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR -6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-2 96-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, A kit for detecting gastric cancer, comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089, and miR-671-5p.
[0021] (2) miR-4257 is hsa-miR-4257, miR-6726-5p is hsa-miR-6726-5p, miR-1343-3p is hsa-miR-1343-3p, miR-1247-3p is hsa-miR-1247-3p, miR-6787-5p is hsa-miR-6787-5p, miR-6875-5p is hsa-miR-6875-5p, miR-1225-3p is hsa-miR-1225-3p, miR-8063 is hsa-miR-8063, and miR-6781 -5p is hsa-miR-6781-5p, miR-4746-3p is hsa-miR-4746-3p, miR-1908-5p is hsa-miR-1908-5p, miR-6756-5p is hsa-miR-6756-5p, miR-204-3p is hsa-miR-204-3p, miR-4651 is hsa-miR-4651, miR-6757-5p is hsa-miR-6757-5p, miR-6825-5p is hsa-miR-6825-5p, and miR-7108-5p is hsa- miR-7108-5p, miR-4792 is hsa-miR-4792, miR-7641 is hsa-miR-7641, miR-3188 is hsa-miR-3188, miR-3131 is hsa-miR-3131, miR-6780b-5p is hsa-miR-6780b-5p, miR-8069 is hsa-miR-8069, miR-6840-3p is hsa-miR-6840-3p, miR-8072 is hsa-miR-8072, and miR-1233-5p is hsa-miR -1233-5p, miR-6887-5p is hsa-miR-6887-5p, miR-1231 is hsa-miR-1231, miR-5572 is hsa-miR-5572, miR-6738-5p is hsa-miR-6738-5p, miR-6784-5p is hsa-miR-6784-5p, miR-6791-5p is hsa-miR-6791-5p, miR-6749-5p is hsa-miR-6749-5p, miR-6741-5p is hsa-miR-6741-5p,miR-128-1-5p is hsa-miR-128-1-5p, miR-4419b is hsa-miR-4419b, miR-6746-5p is hsa-miR-6746-5p, miR-3184-5p is hsa-miR-3184-5p, miR-3679-5p is hsa-miR-3679-5p, miR-7110-5p is hsa-miR-7110-5p, miR-4516 is hsa-miR-4516, miR-6717-5p is hsa-miR-6717-5p, and miR -6826-5p is hsa-miR-6826-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-3679-3p is hsa-miR-3679-3p, miR-3135b is hsa-miR-3135b, miR-3622a-5p is hsa-miR-3622a-5p, miR-711 is hsa-miR-711, miR-4467 is hsa-miR-4467, miR-6857-5p is hsa-miR-6857-5p, and miR-6515-3p is hsa-miR-6515-3p, miR-1225-5p, miR-187-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, and miR-1228-3p. miR-939-5p is hsa-miR-939-5p, miR-6845-5p is hsa-miR-6845-5p, miR-887-3p is hsa-miR-887-3p, miR-7845-5p is hsa-miR-7845-5p, miR-6729-5p is hsa-miR-6729-5p, miR-4632-5p is hsa-miR-4632-5p, miR-615-5p is hsa-miR-615-5p, miR-6724-5p is hsa-miR-6724-5p,miR-4728-5p is hsa-miR-4728-5p, miR-6732-5p is hsa-miR-6732-5p, miR-6816-5p is hsa-miR-6816-5p, miR-4695-5p is hsa-miR-4695-5p, miR-6088 is hsa-miR-6088, miR-7975 is hsa-miR-7975, miR-3197 is hsa-miR-3197, miR-6125 is hsa-miR-6125, and miR-4433-3p is hsa-miR-44 33-3p, miR-6727-5p is hsa-miR-6727-5p, miR-4706 is hsa-miR-4706, miR-7847-3p is hsa-miR-7847-3p, miR-6805-3p is hsa-miR-6805-3p, miR-6766-3p is hsa-miR-6766-3p, miR-1913 is hsa-miR-1913, miR-4649-5p is hsa-miR-4649-5p, miR-602 is hsa-miR-602, and miR-3663-3p are p is hsa-miR-3663-3p, miR-6893-5p is hsa-miR-6893-5p, miR-6861-5p is hsa-miR-6861-5p, miR-4449 is hsa-miR-4449, miR-6842-5p is hsa-miR-6842-5p, miR-4454 is hsa-miR-4454, miR-5195-3p is hsa-miR-5195-3p, miR-663b is hsa-miR-663b, and miR-6765-5p is hsa-miR-6765-5p , miR-4513 is hsa-miR-4513, miR-614 is hsa-miR-614, miR-6785-5p is hsa-miR-6785-5p, miR-6777-5p is hsa-miR-6777-5p, miR-940 is hsa-miR-940, miR-4741 is hsa-miR-4741, miR-6870-5p is hsa-miR-6870-5p, miR-6131 is hsa-miR-6131, and miR-150-3p is hsa-miR-150-3p;miR-4707-5p is hsa-miR-4707-5p, miR-1915-3p is hsa-miR-1915-3p, miR-3937 is hsa-miR-3937, miR-937-5p is hsa-miR-937-5p, miR-4443 is hsa-miR-4443, miR-1914-3p is hsa-miR-1914-3p, miR-3620-5p is hsa-miR-3620-5p, miR-1268b is hsa-miR-1268b, and miR-1227-5p is hsa-miR -1227-5p, miR-6880-5p is hsa-miR-6880-5p, miR-4417 is hsa-miR-4417, miR-6802-5p is hsa-miR-6802-5p, miR-6769a-5p is hsa-miR-6769a-5p, miR-663a is hsa-miR-663a, miR-6721-5p is hsa-miR-6721-5p, miR-4532 is hsa-miR-4532, miR-7977 is hsa-miR-7977, and miR-92b-5p is hsa-miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-4665-3p, miR-423-5p, miR-1469, miR-1469, miR-4675, miR-1915-5p, miR-1915-5p, and miR-6716- 5p is hsa-miR-6716-5p, miR-718 is hsa-miR-718, miR-4281 is hsa-miR-4281, miR-6820-5p is hsa-miR-6820-5p, miR-6795-5p is hsa-miR-6795-5p, miR-6779-5p is hsa-miR-6779-5p, miR-7109-5p is hsa-miR-7109-5p, miR-6798-5p is hsa-miR-6798-5p, miR-4648 is hsa-miR-4648,miR-8059 is hsa-miR-8059, miR-6765-3p is hsa-miR-6765-3p, miR-6132 is hsa-miR-6132, miR-4492 is hsa-miR-4492, miR-7107-5p is hsa-miR-7107-5p, miR-3195 is hsa-miR-3195, miR-3180 is hsa-miR-3180, miR-296-3p is hsa-miR-296-3p, miR-564 is hsa-miR-564, and miR-1268 a is hsa-miR-1268a, miR-6848-5p is hsa-miR-6848-5p, miR-762 is hsa-miR-762, miR-2861 is hsa-miR-2861, miR-1203 is hsa-miR-1203, miR-1260b is hsa-miR-1260b, miR-4476 is hsa-miR-4476, miR-6885-5p is hsa-miR-6885-5p, miR-6769b-5p is hsa-miR-6769b-5p, and miR-23b-3 p is hsa-miR-23b-3p, miR-1343-5p is hsa-miR-1343-5p, miR-3621 is hsa-miR-3621, miR-4688 is hsa-miR-4688, miR-4286 is hsa-miR-4286, miR-4640-5p is hsa-miR-4640-5p, miR-4739 is hsa-miR-4739, miR-1260a is hsa-miR-1260a, miR-4276 is hsa-miR-4276, and miR-7106-5p is hsa-miR-3621. a-miR-7106-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6774-5p is hsa-miR-6774-5p, miR-4707-3p is hsa-miR-4707-3p, miR-4534 is hsa-miR-4534, miR-4294 is hsa-miR-4294, miR-6850-5p is hsa-miR-6850-5p, miR-6089 is hsa-miR-6089, and miR-671-5p is hsa-miR-671-5p;The kit according to (1).
[0022] (3) The nucleic acid is a polynucleotide shown in (a) to (e) below: (a) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a base sequence in which u is t in the base sequence, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (b) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642; (c) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a base sequence complementary to the base sequence in which u is t in the base sequence, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a base sequence in which u is t in the base sequence; and (e) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d); The kit according to (1) or (2), wherein the polynucleotide is selected from the group consisting of:
[0023] (4) The kit according to any one of (1) to (3), further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of other gastric cancer markers, miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, and miR-486-3p.
[0024] (5) The kit according to (4), wherein miR-128-2-5p is hsa-miR-128-2-5p, miR-125a-3p is hsa-miR-125a-3p, miR-92a-2-5p is hsa-miR-92a-2-5p, and miR-486-3p is hsa-miR-486-3p.
[0025] (6) The nucleic acid is a polynucleotide shown in (f) to (j) below: (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 166 to 169 or a base sequence in which u is t in the base sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 166 to 169; (h) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any one of SEQ ID NOs: 166 to 169 or a nucleotide sequence in which u is t in the nucleotide sequence; a variant thereof; a derivative thereof; or a fragment thereof comprising 15 or more consecutive nucleotides; (i) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 166 to 169 or a base sequence in which u is t in the base sequence; and (j) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i); The kit according to (4) or (5), wherein the polynucleotide is selected from the group consisting of:
[0026] (7) The kit is for use in detecting another gastric cancer marker, such as miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, or miR-6782-5p. The kit according to any one of (1) to (6), further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141, and miR-1199-5p.
[0027] (8) miR-3196 is hsa-miR-3196, miR-211-3p is hsa-miR-211-3p, miR-4271 is hsa-miR-4271, miR-6851-5p is hsa-miR-6851-5p, miR-149-3p is hsa-miR-149-3p, miR-4667-5p is hsa-miR-4667-5p, miR-135a-3p is hsa-miR-135a-3p, and miR-4486 is hsa-mi miR-4486, miR-4697-5p is hsa-miR-4697-5p, miR-4725-3p is hsa-miR-4725-3p, miR-6510-5p is hsa-miR-6510-5p, miR-5001-5p is hsa-miR-5001-5p, miR-4673 is hsa-miR-4673, miR-4466 is hsa-miR-4466, miR-23a-3p is hsa-miR-23a-3p, and miR-36 56 is hsa-miR-3656, miR-6782-5p is hsa-miR-6782-5p, miR-4689 is hsa-miR-4689, miR-451a is hsa-miR-451a, miR-4446-3p is hsa-miR-4446-3p, miR-3180-3p is hsa-miR-3180-3p, miR-642a-3p is hsa-miR-642a-3p, and miR-6889-5p is hsa-miR-6889-5 p, miR-3178 is hsa-miR-3178, miR-4665-5p is hsa-miR-4665-5p, miR-6722-3p is hsa-miR-6722-3p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-4507 is hsa-miR-4507, miR-3141 is hsa-miR-3141, and miR-1199-5p is hsa-miR-1199-5p. (7) The kit according to claim 7,
[0028] (9) The nucleic acid is a polynucleotide represented by any one of (k) to (o) below: (k) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 170 to 199 or a base sequence in which u is t in the base sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 170 to 199; (m) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 170 to 199 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence; a variant thereof; a derivative thereof; or a fragment thereof comprising 15 or more consecutive nucleotides; (n) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 170 to 199 or a base sequence in which u is t in the base sequence; and (o) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (k) to (n); The kit according to (7) or (8), wherein the polynucleotide is selected from the group consisting of:
[0029] (10) A kit according to any one of (1) to (9), comprising at least two or more nucleic acids capable of specifically binding to each of at least two or more polynucleotides selected from all of the gastric cancer markers according to (1) or (2).
[0030] (11) miR-4257, miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, which are gastric cancer markersmiR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR- 6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, mi R-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, mi R-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR- 6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-29 6-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, m A device for detecting gastric cancer, comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of iR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089, and miR-671-5p.
[0031] (12) miR-4257 is hsa-miR-4257, miR-6726-5p is hsa-miR-6726-5p, miR-1343-3p is hsa-miR-1343-3p, miR-1247-3p is hsa-miR-1247-3p, miR-6787-5p is hsa-miR-6787-5p, miR-6875-5p is hsa-miR-6875-5p, miR-1225-3p is hsa-miR-1225-3p, miR-8063 is hsa-miR-8063, and miR-6781 -5p is hsa-miR-6781-5p, miR-4746-3p is hsa-miR-4746-3p, miR-1908-5p is hsa-miR-1908-5p, miR-6756-5p is hsa-miR-6756-5p, miR-204-3p is hsa-miR-204-3p, miR-4651 is hsa-miR-4651, miR-6757-5p is hsa-miR-6757-5p, miR-6825-5p is hsa-miR-6825-5p, and miR-7108-5p is hsa- miR-7108-5p, miR-4792 is hsa-miR-4792, miR-7641 is hsa-miR-7641, miR-3188 is hsa-miR-3188, miR-3131 is hsa-miR-3131, miR-6780b-5p is hsa-miR-6780b-5p, miR-8069 is hsa-miR-8069, miR-6840-3p is hsa-miR-6840-3p, miR-8072 is hsa-miR-8072, and miR-1233-5p is hsa-miR -1233-5p, miR-6887-5p is hsa-miR-6887-5p, miR-1231 is hsa-miR-1231, miR-5572 is hsa-miR-5572, miR-6738-5p is hsa-miR-6738-5p, miR-6784-5p is hsa-miR-6784-5p, miR-6791-5p is hsa-miR-6791-5p, miR-6749-5p is hsa-miR-6749-5p, miR-6741-5p is hsa-miR-6741-5p,miR-128-1-5p is hsa-miR-128-1-5p, miR-4419b is hsa-miR-4419b, miR-6746-5p is hsa-miR-6746-5p, miR-3184-5p is hsa-miR-3184-5p, miR-3679-5p is hsa-miR-3679-5p, miR-7110-5p is hsa-miR-7110-5p, miR-4516 is hsa-miR-4516, miR-6717-5p is hsa-miR-6717-5p, and miR -6826-5p is hsa-miR-6826-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-3679-3p is hsa-miR-3679-3p, miR-3135b is hsa-miR-3135b, miR-3622a-5p is hsa-miR-3622a-5p, miR-711 is hsa-miR-711, miR-4467 is hsa-miR-4467, miR-6857-5p is hsa-miR-6857-5p, and miR-6515-3p is hsa-miR-6515-3p, miR-1225-5p, miR-187-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, and miR-1228-3p. miR-939-5p is hsa-miR-939-5p, miR-6845-5p is hsa-miR-6845-5p, miR-887-3p is hsa-miR-887-3p, miR-7845-5p is hsa-miR-7845-5p, miR-6729-5p is hsa-miR-6729-5p, miR-4632-5p is hsa-miR-4632-5p, miR-615-5p is hsa-miR-615-5p, miR-6724-5p is hsa-miR-6724-5p,miR-4728-5p is hsa-miR-4728-5p, miR-6732-5p is hsa-miR-6732-5p, miR-6816-5p is hsa-miR-6816-5p, miR-4695-5p is hsa-miR-4695-5p, miR-6088 is hsa-miR-6088, miR-7975 is hsa-miR-7975, miR-3197 is hsa-miR-3197, miR-6125 is hsa-miR-6125, and miR-4433-3p is hsa-miR-44 33-3p, miR-6727-5p is hsa-miR-6727-5p, miR-4706 is hsa-miR-4706, miR-7847-3p is hsa-miR-7847-3p, miR-6805-3p is hsa-miR-6805-3p, miR-6766-3p is hsa-miR-6766-3p, miR-1913 is hsa-miR-1913, miR-4649-5p is hsa-miR-4649-5p, miR-602 is hsa-miR-602, and miR-3663-3p are p is hsa-miR-3663-3p, miR-6893-5p is hsa-miR-6893-5p, miR-6861-5p is hsa-miR-6861-5p, miR-4449 is hsa-miR-4449, miR-6842-5p is hsa-miR-6842-5p, miR-4454 is hsa-miR-4454, miR-5195-3p is hsa-miR-5195-3p, miR-663b is hsa-miR-663b, and miR-6765-5p is hsa-miR-6765-5p , miR-4513 is hsa-miR-4513, miR-614 is hsa-miR-614, miR-6785-5p is hsa-miR-6785-5p, miR-6777-5p is hsa-miR-6777-5p, miR-940 is hsa-miR-940, miR-4741 is hsa-miR-4741, miR-6870-5p is hsa-miR-6870-5p, miR-6131 is hsa-miR-6131, and miR-150-3p is hsa-miR-150-3p;miR-4707-5p is hsa-miR-4707-5p, miR-1915-3p is hsa-miR-1915-3p, miR-3937 is hsa-miR-3937, miR-937-5p is hsa-miR-937-5p, miR-4443 is hsa-miR-4443, miR-1914-3p is hsa-miR-1914-3p, miR-3620-5p is hsa-miR-3620-5p, miR-1268b is hsa-miR-1268b, and miR-1227-5p is hsa-miR -1227-5p, miR-6880-5p is hsa-miR-6880-5p, miR-4417 is hsa-miR-4417, miR-6802-5p is hsa-miR-6802-5p, miR-6769a-5p is hsa-miR-6769a-5p, miR-663a is hsa-miR-663a, miR-6721-5p is hsa-miR-6721-5p, miR-4532 is hsa-miR-4532, miR-7977 is hsa-miR-7977, and miR-92b-5p is hsa-miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-4665-3p, miR-423-5p, miR-1469, miR-1469, miR-4675, miR-1915-5p, miR-1915-5p, and miR-6716- 5p is hsa-miR-6716-5p, miR-718 is hsa-miR-718, miR-4281 is hsa-miR-4281, miR-6820-5p is hsa-miR-6820-5p, miR-6795-5p is hsa-miR-6795-5p, miR-6779-5p is hsa-miR-6779-5p, miR-7109-5p is hsa-miR-7109-5p, miR-6798-5p is hsa-miR-6798-5p, miR-4648 is hsa-miR-4648,miR-8059 is hsa-miR-8059, miR-6765-3p is hsa-miR-6765-3p, miR-6132 is hsa-miR-6132, miR-4492 is hsa-miR-4492, miR-7107-5p is hsa-miR-7107-5p, miR-3195 is hsa-miR-3195, miR-3180 is hsa-miR-3180, miR-296-3p is hsa-miR-296-3p, miR-564 is hsa-miR-564, and miR-1268 a is hsa-miR-1268a, miR-6848-5p is hsa-miR-6848-5p, miR-762 is hsa-miR-762, miR-2861 is hsa-miR-2861, miR-1203 is hsa-miR-1203, miR-1260b is hsa-miR-1260b, miR-4476 is hsa-miR-4476, miR-6885-5p is hsa-miR-6885-5p, miR-6769b-5p is hsa-miR-6769b-5p, and miR-23b-3 p is hsa-miR-23b-3p, miR-1343-5p is hsa-miR-1343-5p, miR-3621 is hsa-miR-3621, miR-4688 is hsa-miR-4688, miR-4286 is hsa-miR-4286, miR-4640-5p is hsa-miR-4640-5p, miR-4739 is hsa-miR-4739, miR-1260a is hsa-miR-1260a, miR-4276 is hsa-miR-4276, and miR-7106-5p is hsa-miR-3621. a-miR-7106-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6774-5p is hsa-miR-6774-5p, miR-4707-3p is hsa-miR-4707-3p, miR-4534 is hsa-miR-4534, miR-4294 is hsa-miR-4294, miR-6850-5p is hsa-miR-6850-5p, miR-6089 is hsa-miR-6089, and miR-671-5p is hsa-miR-671-5p;The device according to (11).
[0032] (13) The nucleic acid is a polynucleotide shown in any one of (a) to (e) below: (a) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a base sequence in which u is t in the base sequence, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (b) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642; (c) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a base sequence complementary to the base sequence in which u is t in the base sequence, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a base sequence in which u is t in the base sequence; and (e) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d); The device according to (11) or (12), wherein the polynucleotide is selected from the group consisting of:
[0033] (14) The device according to any one of (11) to (13), further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of other gastric cancer markers: miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, and miR-486-3p.
[0034] (15) The device according to (14), wherein miR-128-2-5p is hsa-miR-128-2-5p, miR-125a-3p is hsa-miR-125a-3p, miR-92a-2-5p is hsa-miR-92a-2-5p, and miR-486-3p is hsa-miR-486-3p.
[0035] (16) The nucleic acid is a polynucleotide shown in (f) to (j) below: (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 166 to 169 or a base sequence in which u is t in the base sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 166 to 169; (h) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any one of SEQ ID NOs: 166 to 169 or a nucleotide sequence in which u is t in the nucleotide sequence; a variant thereof; a derivative thereof; or a fragment thereof comprising 15 or more consecutive nucleotides; (i) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 166 to 169 or a base sequence in which u is t in the base sequence; and (j) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i); The device according to (14) or (15), wherein the polynucleotide is selected from the group consisting of:
[0036] (17) The device is configured to detect other gastric cancer markers, such as miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, and miR- The device according to any one of (11) to (16), further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141, and miR-1199-5p.
[0037] (18) miR-3196 is hsa-miR-3196, miR-211-3p is hsa-miR-211-3p, miR-4271 is hsa-miR-4271, miR-6851-5p is hsa-miR-6851-5p, miR-149-3p is hsa-miR-149-3p, miR-4667-5p is hsa-miR-4667-5p, miR-135a-3p is hsa-miR-135a-3p, and miR-4486 is hsa-mi miR-4486, miR-4697-5p is hsa-miR-4697-5p, miR-4725-3p is hsa-miR-4725-3p, miR-6510-5p is hsa-miR-6510-5p, miR-5001-5p is hsa-miR-5001-5p, miR-4673 is hsa-miR-4673, miR-4466 is hsa-miR-4466, miR-23a-3p is hsa-miR-23a-3p, and miR-365 6 is hsa-miR-3656, miR-6782-5p is hsa-miR-6782-5p, miR-4689 is hsa-miR-4689, miR-451a is hsa-miR-451a, miR-4446-3p is hsa-miR-4446-3p, miR-3180-3p is hsa-miR-3180-3p, miR-642a-3p is hsa-miR-642a-3p, and miR-6889-5p is hsa-miR-6889-5p. The device according to (17), wherein miR-3178 is hsa-miR-3178, miR-4665-5p is hsa-miR-4665-5p, miR-6722-3p is hsa-miR-6722-3p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-4507 is hsa-miR-4507, miR-3141 is hsa-miR-3141, and miR-1199-5p is hsa-miR-1199-5p.
[0038] (19) The nucleic acid is a polynucleotide shown in (k) to (o) below: (k) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 170 to 199 or a base sequence in which u is t in the base sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 170 to 199; (m) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 170 to 199 or a nucleotide sequence complementary to the nucleotide sequence in which u is t in the nucleotide sequence; a variant thereof; a derivative thereof; or a fragment thereof comprising 15 or more consecutive nucleotides; (n) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 177 to 199 or a base sequence in which u is t in the base sequence; and (o) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (k) to (n); The device according to (17) or (18), wherein the polynucleotide is selected from the group consisting of:
[0039] (20) The device according to any one of (11) to (19), which is a device for measurement by hybridization technology.
[0040] (21) The device according to (20), wherein the hybridization technology is a nucleic acid array technology.
[0041] (22) The device according to any one of (11) to (21), comprising at least two or more nucleic acids capable of specifically binding to each of at least two or more polynucleotides selected from all of the gastric cancer markers according to (11) or (12).
[0042] (23) A method for detecting stomach cancer, comprising measuring the expression level of a target nucleic acid in a specimen from a subject using a kit according to any one of (1) to (10) or a device according to any one of (11) to (22), and evaluating in vitro whether the subject is affected with stomach cancer or not using the measured expression level and a control expression level similarly measured in a healthy subject.
[0043] (24) The method according to (23), wherein the subject is a human.
[0044] (25) The method according to (23) or (24), wherein the sample is blood, serum, or plasma.
[0045] <Terminology> Terms used herein have the following definitions.
[0046] The abbreviations for nucleotide, polynucleotide, DNA, RNA, etc. shall be in accordance with the "Guidelines for the Preparation of Specifications Including Nucleotide Sequences or Amino Acid Sequences" (edited by the Japan Patent Office) and common practice in the technical field.
[0047] As used herein, the term "polynucleotide" refers to nucleic acids, including RNA, DNA, and RNA / DNA chimeras. DNA includes cDNA, genomic DNA, and synthetic DNA. RNA includes total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA, and synthetic RNA. As used herein, "synthetic DNA" and "synthetic RNA" refer to DNA and RNA artificially produced using, for example, an automated nucleic acid synthesizer based on a predetermined base sequence (whether a natural or non-natural sequence). As used herein, the term "non-natural sequence" is intended to be used in a broad sense and includes sequences that differ from a natural sequence, such as sequences containing one or more nucleotide substitutions, deletions, insertions, and / or additions (i.e., mutant sequences), sequences containing one or more modified nucleotides (i.e., modified sequences), and the like. As used herein, the term "polynucleotide" is used interchangeably with the term "nucleic acid."
[0048] As used herein, a "fragment" refers to a polynucleotide having a continuous partial base sequence of a polynucleotide, and desirably has a length of 15 bases or more, preferably 17 bases or more, and more preferably 19 bases or more.
[0049] As used herein, the term "gene" is intended to encompass not only RNA and double-stranded DNA, but also each of the single-stranded DNAs that constitute them, such as the positive strand (or sense strand) or complementary strand (or antisense strand), and is not particularly limited by its length.
[0050] Therefore, unless otherwise specified, the term "gene" as used herein includes double-stranded DNA, including human genomic DNA, single-stranded DNA (positive strand), single-stranded DNA (complementary strand, including cDNA) having a sequence complementary to the positive strand, microRNA (miRNA), and any of their fragments and transcription products. Furthermore, the term "gene" encompasses not only "genes" represented by specific nucleotide sequences (or SEQ ID NO: 1), but also "nucleic acids" encoding RNAs with biological functions equivalent to the RNAs encoded by these sequences, such as homologs (i.e., homologs or orthologs), variants such as genetic polymorphisms, and derivatives. Specific examples of "nucleic acids" encoding such homologs, variants, or derivatives include "nucleic acids" having a nucleotide sequence that hybridizes under stringent conditions described below with a nucleotide sequence represented by any of SEQ ID NOs: 1 to 657, or with a complementary sequence of the nucleotide sequence in which u is replaced by t. The term "gene" does not limit the scope of functional regions, and may include, for example, expression control regions, coding regions, exons, or introns. Furthermore, the "gene" may be contained within the cell, may be released outside the cell and exist independently, or may be encapsulated in a vesicle called an exosome.
[0051] As used herein, "exosomes" (also known as "exosomes") are small vesicles enclosed in a lipid bilayer membrane that are secreted from cells. Exosomes are derived from multivesicular endosomes and, when released into the extracellular environment, may contain biological substances such as RNA, DNA, and other "genes" and proteins. Exosomes are known to be contained in body fluids such as blood, serum, plasma, and lymph.
[0052] As used herein, the term "transcription product" refers to RNA synthesized using the DNA sequence of a gene as a template. RNA polymerase binds to a site called the promoter located upstream of the gene, and RNA is synthesized by attaching ribonucleotides to the 3' end so that the sequence is complementary to the DNA base sequence. This RNA includes not only the gene itself, but also the entire sequence from the transcription start point to the end of the poly(A) sequence, including expression control regions, coding regions, exons, and introns.
[0053] Unless otherwise specified, the term "microRNA (miRNA)" as used herein refers to a 15- to 25-base non-coding RNA that is transcribed as a hairpin-like RNA precursor, cleaved by a dsRNA cleaving enzyme with RNase III cleavage activity, incorporated into a protein complex called RISC, and involved in mRNA translational repression. The term "miRNA" as used herein encompasses not only "miRNA" represented by a specific nucleotide sequence (or SEQ ID NO:), but also precursors of the "miRNA" (pre-miRNA, pri-miRNA), miRNAs with equivalent biological functions, such as homologs (i.e., homologs or orthologs), variants such as genetic polymorphisms, and derivatives. Specific examples of such precursors, homologs, variants, or derivatives include "miRNAs" that can be identified using miRBase release 20 (http: / / www.mirbase.org / ) and have a nucleotide sequence that hybridizes to the complementary sequence of any of the specific nucleotide sequences represented by SEQ ID NOs: 1 to 657 under stringent conditions, as described below. Furthermore, as used herein, "miRNA" may refer to the gene product of a miR gene, and such gene products include mature miRNAs (e.g., non-coding RNAs of 15 to 25 bases or 19 to 25 bases involved in translational repression of mRNA as described above) or miRNA precursors (e.g., pre-miRNAs or pri-miRNAs as described above).
[0054] As used herein, the term "probe" encompasses a polynucleotide used to specifically detect RNA produced by gene expression or a polynucleotide derived therefrom, and / or a polynucleotide complementary thereto.
[0055] As used herein, the term "primer" encompasses a polynucleotide that specifically recognizes and amplifies RNA generated by gene expression or a polynucleotide derived therefrom, and / or a polynucleotide complementary thereto.
[0056] Here, a complementary polynucleotide (complementary strand, reverse strand) refers to a polynucleotide that is base-complementary to the full-length polynucleotide sequence consisting of a base sequence defined by any one of SEQ ID NOS: 1 to 657, or a base sequence in which u is replaced with t, or a partial sequence thereof (herein referred to as the normal strand for convenience). However, such a complementary strand is not limited to a sequence that forms a completely complementary sequence with the base sequence of the target normal strand, and may have a complementary relationship to the extent that it can hybridize with the target normal strand under stringent conditions.
[0057] As used herein, "stringent conditions" refers to conditions under which a nucleic acid probe hybridizes to its target sequence to a greater extent than to other sequences (e.g., a measurement value of at least the average of background measurements plus twice the standard error of the background measurement). Stringent conditions are sequence-dependent and vary depending on the environment in which hybridization occurs. By controlling the stringency of hybridization and / or washing conditions, a target sequence that is 100% complementary to a nucleic acid probe can be identified. Specific examples of "stringent conditions" are described below.
[0058] As used herein, the term "Tm value" refers to the temperature at which the double-stranded portion of a polynucleotide is denatured into single strands, and the double-stranded and single-stranded portions exist in a 1:1 ratio.
[0059] As used herein, the term "variant" refers to, in the case of nucleic acids, natural variants resulting from polymorphism, mutation, etc., or variants containing deletion, substitution, addition, or insertion of one or more bases in any of the base sequences of SEQ ID NOs: 1 to 657, or in which u is replaced with t in said base sequence, or in a partial sequence thereof; variants showing % identity with each of said base sequences or a partial sequence thereof of about 90% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more; or nucleic acids that hybridize under stringent conditions as defined above to polynucleotides or oligonucleotides containing said base sequence or a partial sequence thereof.
[0060] As used herein, "several" means an integer of about 10, 9, 8, 7, 6, 5, 4, 3, or 2.
[0061] As used herein, mutants can be prepared using well-known techniques such as site-directed mutagenesis and PCR-assisted mutagenesis.
[0062] As used herein, "% identity" can be determined using the above-mentioned BLAST or FASTA protein or gene search systems, with or without introducing gaps (Zheng Zhang et al., 2000, J. Comput. Biol., Vol. 7, pp. 203-214; Altschul, S.F. et al., 1990, Journal of Molecular Biology, Vol. 215, pp. 403-410; Pearson, W.R. et al., 1988, Proc. Natl. Acad. Sci. USA, Vol. 85, pp. 2444-2448).
[0063] As used herein, the term "derivative" refers to modified nucleic acids, including, but not limited to, derivatives labeled with a fluorophore or the like, derivatives containing modified nucleotides (e.g., nucleotides containing groups such as halogen, alkyl such as methyl, alkoxy such as methoxy, thio, and carboxymethyl, and nucleotides that have undergone base rearrangement, double bond saturation, deamination, or substitution of oxygen molecules with sulfur molecules), PNA (peptide nucleic acid; Nielsen, P.E. 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), and the like.
[0064] As used herein, a "nucleic acid" capable of specifically binding to a polynucleotide selected from the miRNAs that are gastric cancer markers refers to a synthetic or prepared nucleic acid, specifically including a "nucleic acid probe" or "primer," which is used directly or indirectly to detect the presence or absence of gastric cancer in a subject, to diagnose the presence or absence of gastric cancer, the severity of gastric cancer, the presence or degree of improvement of gastric cancer, or sensitivity to gastric cancer treatment, or to screen for candidate substances useful for the prevention, amelioration, or treatment of gastric cancer. These include nucleotides, oligonucleotides, and polynucleotides that can specifically recognize and bind to a transcription product represented by any of SEQ ID NOs: 1 to 657 or its cDNA synthetic nucleic acid in a sample in vivo, particularly in a body fluid such as blood or urine, in relation to gastric cancer. Based on the above properties, these nucleotides, oligonucleotides, and polynucleotides can be effectively used as probes for detecting the above genes expressed in vivo, in tissues, cells, etc., or as primers for amplifying the above genes expressed in vivo.
[0065] The term "detection" as used herein may be replaced with the terms "test," "measurement," "detection," or "assistance in diagnosis." Furthermore, the term "evaluation" as used herein is used to mean assisting diagnosis or assessment based on test results or measurement results.
[0066] As used herein, "subject" refers to mammals such as humans, primates including chimpanzees, pet animals such as dogs and cats, livestock animals such as cows, horses, sheep and goats, and rodents such as mice and rats. A "healthy subject" also refers to such mammals that are not affected by the cancer to be detected.
[0067] As used herein, "P" or "P value" indicates the probability that a statistical value that is more extreme than the statistical value actually calculated from data under the null hypothesis will be observed in a statistical test. Therefore, the smaller the "P" or "P value," the more significant the difference between the compared subjects.
[0068] As used herein, "sensitivity" refers to the value of (number of true positives) / (number of true positives + number of false negatives). High sensitivity enables early detection of gastric cancer, leading to complete resection of cancerous tissue and a reduced recurrence rate.
[0069] As used herein, "specificity" means (number of true negatives) / (number of true negatives + number of false positives). High specificity prevents unnecessary additional testing due to misidentification of healthy subjects as stomach cancer patients, reducing the burden on patients and medical costs.
[0070] In this specification, "accuracy" means the value of (number of true positives + number of true negatives) / (total number of cases). Accuracy indicates the proportion of correct discrimination results for all samples, and is the primary index for evaluating detection performance.
[0071] As used herein, the term "specimen" to be assessed, detected, or diagnosed refers to tissues and biological materials in which the expression of the gene of the present invention changes with the onset, progression, and therapeutic effects of stomach cancer. Specifically, this refers to stomach 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 exudate, as well as serum and plasma prepared from blood, and other fluids such as stool and hair. It also refers to biological samples extracted from these, specifically genes such as RNA and miRNA.
[0072] As used herein, the term "hsa-miR-4257 gene" or "hsa-miR-4257" encompasses the hsa-miR-4257 gene set forth in SEQ ID NO: 1 (miRBase Accession No. MIMAT0016878) as well as homologs or orthologs from other biological species. The hsa-miR-4257 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, vol. 4, e7192. Furthermore, a known precursor of "hsa-miR-4257" is "hsa-mir-4257" (miRBase Accession No. MI0015856, SEQ ID NO: 200), which has a hairpin-like structure.
[0073] As used herein, the term "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" encompasses the hsa-miR-6726-5p gene set forth in SEQ ID NO: 2 (miRBase Accession No. MIMAT0027353) as well as homologs or orthologs from other organisms. The hsa-miR-6726-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6726-5p" is known to be "hsa-mir-6726" (miRBase Accession No. MI0022571, SEQ ID NO: 201), which has a hairpin-like structure.
[0074] As used herein, the terms "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" encompass the hsa-miR-1343-3p gene set forth in SEQ ID NO: 3 (miRBase Accession No. MIMAT0019776) as well as homologs or orthologs from other species. The hsa-miR-1343-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, the precursor of "hsa-miR-1343-3p" is known to be "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 202), which has a hairpin-like structure.
[0075] As used herein, the terms "hsa-miR-1247-3p gene" or "hsa-miR-1247-3p" encompass the hsa-miR-1247-3p gene set forth in SEQ ID NO: 4 (miRBase Accession No. MIMAT0022721) as well as homologs or orthologs from other organisms. The hsa-miR-1247-3p gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, vol. 18, pp. 610-621. Furthermore, the precursor of "hsa-miR-1247-3p" is known to be "hsa-mir-1247" (miRBase Accession No. MI0006382, SEQ ID NO: 203), which has a hairpin-like structure.
[0076] As used herein, the term "hsa-miR-6787-5p gene" or "hsa-miR-6787-5p" encompasses the hsa-miR-6787-5p gene set forth in SEQ ID NO: 5 (miRBase Accession No. MIMAT0027474) as well as homologs or orthologs from other organisms. The hsa-miR-6787-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6787-5p" is known to be "hsa-mir-6787" (miRBase Accession No. MI0022632, SEQ ID NO: 204), which has a hairpin-like structure.
[0077] As used herein, the term "hsa-miR-6875-5p gene" or "hsa-miR-6875-5p" encompasses the hsa-miR-6875-5p gene set forth in SEQ ID NO: 6 (miRBase Accession No. MIMAT0027650) as well as homologs or orthologs from other organisms. The hsa-miR-6875-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6875-5p" is known to be "hsa-mir-6875" (miRBase Accession No. MI0022722, SEQ ID NO: 205), which has a hairpin-like structure.
[0078] As used herein, the term "hsa-miR-1225-3p gene" or "hsa-miR-1225-3p" encompasses the hsa-miR-1225-3p gene set forth in SEQ ID NO: 7 (miRBase Accession No. MIMAT0005573) as well as homologs or orthologs from other organisms. The hsa-miR-1225-3p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, vol. 28, pp. 328-336. It is also known that the precursor of "hsa-miR-1225-3p" is "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 206), which has a hairpin-like structure.
[0079] As used herein, the term "hsa-miR-8063 gene" or "hsa-miR-8063" encompasses the hsa-miR-8063 gene set forth in SEQ ID NO: 8 (miRBase Accession No. MIMAT0030990) as well as homologs or orthologs from other organisms. The hsa-miR-8063 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, vol. 39, pp. 480-487. Furthermore, a known precursor of "hsa-miR-8063" is "hsa-mir-8063" (miRBase Accession No. MI0025899, SEQ ID NO: 207), which has a hairpin-like structure.
[0080] As used herein, the term "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" encompasses the hsa-miR-6781-5p gene set forth in SEQ ID NO: 9 (miRBase Accession No. MIMAT0027462) and homologs or orthologs from other organisms. The hsa-miR-6781-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6781-5p" is known to be "hsa-mir-6781" (miRBase Accession No. MI0022626, SEQ ID NO: 208), which has a hairpin-like structure.
[0081] As used herein, the term "hsa-miR-4746-3p gene" or "hsa-miR-4746-3p" encompasses the hsa-miR-4746-3p gene set forth in SEQ ID NO: 10 (miRBase Accession No. MIMAT0019881) as well as homologs or orthologs from other organisms. The hsa-miR-4746-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. It is also known that the precursor of "hsa-miR-4746-3p" is "hsa-mir-4746" (miRBase Accession No. MI0017385, SEQ ID NO: 209), which has a hairpin-like structure.
[0082] As used herein, the terms "hsa-miR-1908-5p gene" or "hsa-miR-1908-5p" encompass the hsa-miR-1908-5p gene set forth in SEQ ID NO: 11 (miRBase Accession No. MIMAT0007881) as well as homologs or orthologs from other organisms. The hsa-miR-1908-5p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. It is also known that the precursor of "hsa-miR-1908-5p" is "hsa-mir-1908" (miRBase Accession No. MI0008329, SEQ ID NO: 210), which has a hairpin-like structure.
[0083] As used herein, the term "hsa-miR-6756-5p gene" or "hsa-miR-6756-5p" encompasses the hsa-miR-6756-5p gene set forth in SEQ ID NO: 12 (miRBase Accession No. MIMAT0027412) and homologs or orthologs from other organisms. The hsa-miR-6756-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6756-5p" is known to be "hsa-mir-6756" (miRBase Accession No. MI0022601, SEQ ID NO: 211), which has a hairpin-like structure.
[0084] As used herein, the terms "hsa-miR-204-3p gene" or "hsa-miR-204-3p" encompass the hsa-miR-204-3p gene set forth in SEQ ID NO: 13 (miRBase Accession No. MIMAT0022693) as well as homologs or orthologs from other organisms. The hsa-miR-204-3p gene can be obtained by the method described in Lim LP et al., 2003, Science, vol. 299, p. 1540. It is also known that the precursor of "hsa-miR-204-3p" is "hsa-mir-204" (miRBase Accession No. MI0000284, SEQ ID NO: 212), which has a hairpin-like structure.
[0085] As used herein, the term "hsa-miR-4651 gene" or "hsa-miR-4651" encompasses the hsa-miR-4651 gene set forth in SEQ ID NO: 14 (miRBase Accession No. MIMAT0019715) as well as homologs or orthologs from other organisms. The hsa-miR-4651 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4651" is "hsa-mir-4651" (miRBase Accession No. MI0017279, SEQ ID NO: 213), which has a hairpin-like structure.
[0086] As used herein, the term "hsa-miR-6757-5p gene" or "hsa-miR-6757-5p" encompasses the hsa-miR-6757-5p gene set forth in SEQ ID NO: 15 (miRBase Accession No. MIMAT0027414) as well as homologs or orthologs from other organisms. The hsa-miR-6757-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6757-5p" is known to be "hsa-mir-6757" (miRBase Accession No. MI0022602, SEQ ID NO: 214), which has a hairpin-like structure.
[0087] As used herein, the term "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" encompasses the hsa-miR-6825-5p gene set forth in SEQ ID NO: 16 (miRBase Accession No. MIMAT0027550) and homologs or orthologs from other organisms. The hsa-miR-6825-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6825-5p" is known to be "hsa-mir-6825" (miRBase Accession No. MI0022670, SEQ ID NO: 215), which has a hairpin-like structure.
[0088] As used herein, the term "hsa-miR-7108-5p gene" or "hsa-miR-7108-5p" encompasses the hsa-miR-7108-5p gene set forth in SEQ ID NO: 17 (miRBase Accession No. MIMAT0028113) as well as homologs or orthologs from other organisms. The hsa-miR-7108-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-7108-5p" is known to be "hsa-mir-7108" (miRBase Accession No. MI0022959, SEQ ID NO: 216), which has a hairpin-like structure.
[0089] As used herein, the term "hsa-miR-4792 gene" or "hsa-miR-4792" encompasses the hsa-miR-4792 gene set forth in SEQ ID NO: 18 (miRBase Accession No. MIMAT0019964) as well as homologs or orthologs from other organisms. The hsa-miR-4792 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4792" is "hsa-mir-4792" (miRBase Accession No. MI0017439, SEQ ID NO: 217), which has a hairpin-like structure.
[0090] As used herein, the term "hsa-miR-7641 gene" or "hsa-miR-7641" encompasses the hsa-miR-7641 gene set forth in SEQ ID NO: 19 (miRBase Accession No. MIMAT0029782) as well as homologs or orthologs from other species. The hsa-miR-7641 gene can be obtained by the method described in Yoo JK et al., 2013, Arch Pharm Res, 36, pp. 353-358. Furthermore, "hsa-miR-7641" is known to have precursors with hairpin-like structures, "hsa-mir-7641-1, hsa-mir-7641-2" (miRBase Accession Nos. MI0024975, MI0024976, SEQ ID NOs: 218, 219).
[0091] As used herein, the term "hsa-miR-3188 gene" or "hsa-miR-3188" encompasses the hsa-miR-3188 gene set forth in SEQ ID NO: 20 (miRBase Accession No. MIMAT0015070) as well as homologs or orthologs from other species. The hsa-miR-3188 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. It is also known that "hsa-miR-3188" has a precursor with a hairpin-like structure, "hsa-mir-3188" (miRBase Accession No. MI0014232, SEQ ID NO: 220).
[0092] As used herein, the term "hsa-miR-3131 gene" or "hsa-miR-3131" encompasses the hsa-miR-3131 gene set forth in SEQ ID NO: 21 (miRBase Accession No. MIMAT0014996) as well as homologs or orthologs from other organisms. The hsa-miR-3131 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. It is also known that "hsa-miR-3131" has a precursor, "hsa-mir-3131" (miRBase Accession No. MI0014151, SEQ ID NO: 221), which has a hairpin-like structure.
[0093] As used herein, the term "hsa-miR-6780b-5p gene" or "hsa-miR-6780b-5p" encompasses the hsa-miR-6780b-5p gene set forth in SEQ ID NO: 22 (miRBase Accession No. MIMAT0027572) and homologs or orthologs from other biological species. The hsa-miR-6780b-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6780b-5p" is known to be "hsa-mir-6780b" (miRBase Accession No. MI0022681, SEQ ID NO: 222), which has a hairpin-like structure.
[0094] As used herein, the term "hsa-miR-8069 gene" or "hsa-miR-8069" encompasses the hsa-miR-8069 gene set forth in SEQ ID NO: 23 (miRBase Accession No. MIMAT0030996) as well as homologs or orthologs from other organisms. The hsa-miR-8069 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, vol. 39, pp. 480-487. Furthermore, "hsa-miR-8069" is known to have a precursor, "hsa-mir-8069" (miRBase Accession No. MI0025905, SEQ ID NO: 223), which has a hairpin-like structure.
[0095] As used herein, the term "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" encompasses the hsa-miR-6840-3p gene set forth in SEQ ID NO: 24 (miRBase Accession No. MIMAT0027583) as well as homologs or orthologs from other organisms. The hsa-miR-6840-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6840-3p" is known to be "hsa-mir-6840" (miRBase Accession No. MI0022686, SEQ ID NO: 224), which has a hairpin-like structure.
[0096] As used herein, the term "hsa-miR-8072 gene" or "hsa-miR-8072" encompasses the hsa-miR-8072 gene set forth in SEQ ID NO: 25 (miRBase Accession No. MIMAT0030999) and homologs or orthologs from other organisms. The hsa-miR-8072 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, vol. 39, pp. 480-487. Furthermore, "hsa-miR-8072" is known to have a precursor, "hsa-mir-8072" (miRBase Accession No. MI0025908, SEQ ID NO: 225), which has a hairpin-like structure.
[0097] As used herein, the term "hsa-miR-1233-5p gene" or "hsa-miR-1233-5p" encompasses the hsa-miR-1233-5p gene set forth in SEQ ID NO: 26 (miRBase Accession No. MIMAT0022943) as well as homologs or orthologs from other organisms. The hsa-miR-1233-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, vol. 28, pp. 328-336. Furthermore, "hsa-miR-1233-5p" is known to have precursors with hairpin-like structures, "hsa-mir-1233-1" and "hsa-mir-1233-2" (miRBase Accession Nos. MI0006323 and MI0015973, SEQ ID NOs: 226 and 227).
[0098] As used herein, the term "hsa-miR-6887-5p gene" or "hsa-miR-6887-5p" encompasses the hsa-miR-6887-5p gene set forth in SEQ ID NO: 27 (miRBase Accession No. MIMAT0027674) as well as homologs or orthologs from other organisms. The hsa-miR-6887-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6887-5p" is known to be "hsa-mir-6887" (miRBase Accession No. MI0022734, SEQ ID NO: 228), which has a hairpin-like structure.
[0099] As used herein, the term "hsa-miR-1231 gene" or "hsa-miR-1231" encompasses the hsa-miR-1231 gene set forth in SEQ ID NO: 28 (miRBase Accession No. MIMAT0005586) as well as homologs or orthologs from other organisms. The hsa-miR-1231 gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, vol. 28, pp. 328-336. Furthermore, a known precursor of "hsa-miR-1231" is "hsa-mir-1231" (miRBase Accession No. MI0006321, SEQ ID NO: 229), which has a hairpin-like structure.
[0100] As used herein, the term "hsa-miR-5572 gene" or "hsa-miR-5572" encompasses the hsa-miR-5572 gene set forth in SEQ ID NO: 29 (miRBase Accession No. MIMAT0022260) and homologs or orthologs from other organisms. The hsa-miR-5572 gene can be obtained by the method described in Tandon M et al., 2012, Oral Dis, vol. 18, pp. 127-131. Furthermore, a known precursor of "hsa-miR-5572" is "hsa-mir-5572" (miRBase Accession No. MI0019117, SEQ ID NO: 230), which has a hairpin-like structure.
[0101] As used herein, the term "hsa-miR-6738-5p gene" or "hsa-miR-6738-5p" encompasses the hsa-miR-6738-5p gene set forth in SEQ ID NO: 30 (miRBase Accession No. MIMAT0027377) as well as homologs or orthologs from other organisms. The hsa-miR-6738-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6738-5p" is known to be "hsa-mir-6738" (miRBase Accession No. MI0022583, SEQ ID NO: 231), which has a hairpin-like structure.
[0102] As used herein, the term "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" encompasses the hsa-miR-6784-5p gene set forth in SEQ ID NO: 31 (miRBase Accession No. MIMAT0027468) as well as homologs or orthologs from other organisms. The hsa-miR-6784-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6784-5p" is known to be "hsa-mir-6784" (miRBase Accession No. MI0022629, SEQ ID NO: 232), which has a hairpin-like structure.
[0103] As used herein, the term "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" encompasses the hsa-miR-6791-5p gene set forth in SEQ ID NO: 32 (miRBase Accession No. MIMAT0027482) and homologs or orthologs from other organisms. The hsa-miR-6791-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6791-5p" is known to be "hsa-mir-6791" (miRBase Accession No. MI0022636, SEQ ID NO: 233), which has a hairpin-like structure.
[0104] As used herein, the term "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" encompasses the hsa-miR-6749-5p gene set forth in SEQ ID NO: 33 (miRBase Accession No. MIMAT0027398) as well as homologs or orthologs from other organisms. The hsa-miR-6749-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6749-5p" is known to be "hsa-mir-6749" (miRBase Accession No. MI0022594, SEQ ID NO: 234), which has a hairpin-like structure.
[0105] As used herein, the term "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" encompasses the hsa-miR-6741-5p gene set forth in SEQ ID NO: 34 (miRBase Accession No. MIMAT0027383) as well as homologs or orthologs from other organisms. The hsa-miR-6741-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6741-5p" is known to be "hsa-mir-6741" (miRBase Accession No. MI0022586, SEQ ID NO: 235), which has a hairpin-like structure.
[0106] As used herein, the terms "hsa-miR-128-1-5p gene" or "hsa-miR-128-1-5p" encompass the hsa-miR-128-1-5p gene set forth in SEQ ID NO: 35 (miRBase Accession No. MIMAT0026477) and homologs or orthologs from other organisms. The hsa-miR-128-1-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, vol. 12, pp. 735-739. Furthermore, the precursor of "hsa-miR-128-1-5p" is known to be "hsa-mir-128-1" (miRBase Accession No. MI0000447, SEQ ID NO: 236), which has a hairpin-like structure.
[0107] As used herein, the term "hsa-miR-4419b gene" or "hsa-miR-4419b" encompasses the hsa-miR-4419b gene set forth in SEQ ID NO: 36 (miRBase Accession No. MIMAT0019034) as well as homologs or orthologs from other species. The hsa-miR-4419b gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4419b" is "hsa-mir-4419b" (miRBase Accession No. MI0016861, SEQ ID NO: 237), which has a hairpin-like structure.
[0108] As used herein, the term "hsa-miR-6746-5p gene" or "hsa-miR-6746-5p" encompasses the hsa-miR-6746-5p gene set forth in SEQ ID NO: 37 (miRBase Accession No. MIMAT0027392) and homologs or orthologs from other organisms. The hsa-miR-6746-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6746-5p" is known to be "hsa-mir-6746" (miRBase Accession No. MI0022591, SEQ ID NO: 238), which has a hairpin-like structure.
[0109] As used herein, the terms "hsa-miR-3184-5p gene" or "hsa-miR-3184-5p" encompass the hsa-miR-3184-5p gene set forth in SEQ ID NO: 38 (miRBase Accession No. MIMAT0015064) as well as homologs or orthologs from other species. The hsa-miR-3184-5p gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. It is also known that the precursor of "hsa-miR-3184-5p" is "hsa-mir-3184" (miRBase Accession No. MI0014226, SEQ ID NO: 239), which has a hairpin-like structure.
[0110] As used herein, the term "hsa-miR-3679-5p gene" or "hsa-miR-3679-5p" encompasses the hsa-miR-3679-5p gene set forth in SEQ ID NO: 39 (miRBase Accession No. MIMAT0018104) as well as homologs or orthologs from other organisms. The hsa-miR-3679-5p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, vol. 5, e9637. It is also known that the precursor of "hsa-miR-3679-5p" is "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 240), which has a hairpin-like structure.
[0111] As used herein, the term "hsa-miR-7110-5p gene" or "hsa-miR-7110-5p" encompasses the hsa-miR-7110-5p gene set forth in SEQ ID NO: 40 (miRBase Accession No. MIMAT0028117) as well as homologs or orthologs from other organisms. The hsa-miR-7110-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-7110-5p" is known to be "hsa-mir-7110" (miRBase Accession No. MI0022961, SEQ ID NO: 241), which has a hairpin-like structure.
[0112] As used herein, the term "hsa-miR-4516 gene" or "hsa-miR-4516" encompasses the hsa-miR-4516 gene set forth in SEQ ID NO: 41 (miRBase Accession No. MIMAT0019053) as well as homologs or orthologs from other biological species. The hsa-miR-4516 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4516" is "hsa-mir-4516" (miRBase Accession No. MI0016882, SEQ ID NO: 242), which has a hairpin-like structure.
[0113] As used herein, the term "hsa-miR-6717-5p gene" or "hsa-miR-6717-5p" encompasses the hsa-miR-6717-5p gene set forth in SEQ ID NO: 42 (miRBase Accession No. MIMAT0025846) as well as homologs or orthologs from other organisms. The hsa-miR-6717-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, vol. 497, pp. 330-335. It is also known that the precursor of "hsa-miR-6717-5p" is "hsa-mir-6717" (miRBase Accession No. MI0022551, SEQ ID NO: 243), which has a hairpin-like structure.
[0114] As used herein, the term "hsa-miR-6826-5p gene" or "hsa-miR-6826-5p" encompasses the hsa-miR-6826-5p gene set forth in SEQ ID NO: 43 (miRBase Accession No. MIMAT0027552) and homologs or orthologs from other organisms. The hsa-miR-6826-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6826-5p" is known to be "hsa-mir-6826" (miRBase Accession No. MI0022671, SEQ ID NO: 244), which has a hairpin-like structure.
[0115] As used herein, the term "hsa-miR-4433b-3p gene" or "hsa-miR-4433b-3p" encompasses the hsa-miR-4433b-3p gene set forth in SEQ ID NO: 44 (miRBase Accession No. MIMAT0030414) and homologs or orthologs from other organisms. The hsa-miR-4433b-3p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. It is also known that the precursor of "hsa-miR-4433b-3p" is "hsa-mir-4433b" (miRBase Accession No. MI0025511, SEQ ID NO: 245), which has a hairpin-like structure.
[0116] As used herein, the term "hsa-miR-3679-3p gene" or "hsa-miR-3679-3p" encompasses the hsa-miR-3679-3p gene set forth in SEQ ID NO: 45 (miRBase Accession No. MIMAT0018105) as well as homologs or orthologs from other organisms. The hsa-miR-3679-3p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, vol. 5, e9637. It is also known that the precursor of "hsa-miR-3679-3p" is "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 240), which has a hairpin-like structure.
[0117] As used herein, the term "hsa-miR-3135b gene" or "hsa-miR-3135b" encompasses the hsa-miR-3135b gene set forth in SEQ ID NO: 46 (miRBase Accession No. MIMAT0018985) as well as homologs or orthologs from other species. The hsa-miR-3135b gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-3135b" is "hsa-mir-3135b" (miRBase Accession No. MI0016809, SEQ ID NO: 246), which has a hairpin-like structure.
[0118] As used herein, the term "hsa-miR-3622a-5p gene" or "hsa-miR-3622a-5p" encompasses the hsa-miR-3622a-5p gene set forth in SEQ ID NO: 47 (miRBase Accession No. MIMAT0018003) and homologs or orthologs from other organisms. The hsa-miR-3622a-5p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, vol. 8, p. 58. It is also known that the precursor of "hsa-miR-3622a-5p" is "hsa-mir-3622a" (miRBase Accession No. MI0016013, SEQ ID NO: 247), which has a hairpin-like structure.
[0119] As used herein, the term "hsa-miR-711 gene" or "hsa-miR-711" encompasses the hsa-miR-711 gene set forth in SEQ ID NO: 48 (miRBase Accession No. MIMAT0012734) as well as homologs or orthologs from other species. The hsa-miR-711 gene can be obtained by the method described in Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p. 39. Furthermore, "hsa-miR-711" is known to have a precursor, "hsa-mir-711" (miRBase Accession No. MI0012488, SEQ ID NO: 248), which has a hairpin-like structure.
[0120] As used herein, the term "hsa-miR-4467 gene" or "hsa-miR-4467" encompasses the hsa-miR-4467 gene set forth in SEQ ID NO: 49 (miRBase Accession No. MIMAT0018994) as well as homologs or orthologs from other species. The hsa-miR-4467 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4467" is "hsa-mir-4467" (miRBase Accession No. MI0016818, SEQ ID NO: 249), which has a hairpin-like structure.
[0121] As used herein, the term "hsa-miR-6857-5p gene" or "hsa-miR-6857-5p" encompasses the hsa-miR-6857-5p gene set forth in SEQ ID NO: 50 (miRBase Accession No. MIMAT0027614) and homologs or orthologs from other organisms. The hsa-miR-6857-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6857-5p" is known to be "hsa-mir-6857" (miRBase Accession No. MI0022703, SEQ ID NO: 250), which has a hairpin-like structure.
[0122] As used herein, the term "hsa-miR-6515-3p gene" or "hsa-miR-6515-3p" encompasses the hsa-miR-6515-3p gene set forth in SEQ ID NO: 51 (miRBase Accession No. MIMAT0025487) as well as homologs or orthologs from other organisms. The hsa-miR-6515-3p gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet, vol. 20, pp. 4025-4040. Furthermore, the precursor of "hsa-miR-6515-3p" is known to be "hsa-mir-6515" (miRBase Accession No. MI0022227, SEQ ID NO: 251), which has a hairpin-like structure.
[0123] As used herein, the terms "hsa-miR-1225-5p gene" or "hsa-miR-1225-5p" encompass the hsa-miR-1225-5p gene set forth in SEQ ID NO: 52 (miRBase Accession No. MIMAT0005572) and homologs or orthologs from other organisms. The hsa-miR-1225-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, vol. 28, pp. 328-336. Furthermore, the precursor of "hsa-miR-1225-5p" is known to be "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 206), which has a hairpin-like structure.
[0124] As used herein, the term "hsa-miR-187-5p gene" or "hsa-miR-187-5p" encompasses the hsa-miR-187-5p gene set forth in SEQ ID NO: 53 (miRBase Accession No. MIMAT0004561) and homologs or orthologs from other organisms. The hsa-miR-187-5p gene can be obtained by the method described in Lim LP et al., 2003, Science, vol. 299, p. 1540. It is also known that the precursor of "hsa-miR-187-5p" is "hsa-mir-187" (miRBase Accession No. MI0000274, SEQ ID NO: 252), which has a hairpin-like structure.
[0125] As used herein, the term "hsa-miR-3185 gene" or "hsa-miR-3185" encompasses the hsa-miR-3185 gene set forth in SEQ ID NO: 54 (miRBase Accession No. MIMAT0015065) as well as homologs or orthologs from other organisms. The hsa-miR-3185 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. Furthermore, a known precursor of "hsa-miR-3185" is "hsa-mir-3185" (miRBase Accession No. MI0014227, SEQ ID NO: 253), which has a hairpin-like structure.
[0126] As used herein, the term "hsa-miR-642b-3p gene" or "hsa-miR-642b-3p" encompasses the hsa-miR-642b-3p gene set forth in SEQ ID NO: 55 (miRBase Accession No. MIMAT0018444) and homologs or orthologs from other organisms. The hsa-miR-642b-3p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, vol. 8, p. 58. Furthermore, the precursor of "hsa-miR-642b-3p" is known to be "hsa-mir-642b" (miRBase Accession No. MI0016685, SEQ ID NO: 254), which has a hairpin-like structure.
[0127] As used herein, the term "hsa-miR-1249 gene" or "hsa-miR-1249" encompasses the hsa-miR-1249 gene set forth in SEQ ID NO: 56 (miRBase Accession No. MIMAT0005901) as well as homologs or orthologs from other organisms. The hsa-miR-1249 gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, vol. 18, pp. 610-621. Furthermore, a known precursor of "hsa-miR-1249" is "hsa-mir-1249" (miRBase Accession No. MI0006384, SEQ ID NO: 255), which has a hairpin-like structure.
[0128] As used herein, the term "hsa-miR-744-5p gene" or "hsa-miR-744-5p" encompasses the hsa-miR-744-5p gene set forth in SEQ ID NO: 57 (miRBase Accession No. MIMAT0004945) as well as homologs or orthologs from other organisms. The hsa-miR-744-5p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, vol. 16, pp. 1289-1298. Furthermore, the precursor of "hsa-miR-744-5p" is known to be "hsa-mir-744" (miRBase Accession No. MI0005559, SEQ ID NO: 256), which has a hairpin-like structure.
[0129] As used herein, the term "hsa-miR-4442 gene" or "hsa-miR-4442" encompasses the hsa-miR-4442 gene set forth in SEQ ID NO: 58 (miRBase Accession No. MIMAT0018960) and homologs or orthologs from other biological species. The hsa-miR-4442 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4442" is "hsa-mir-4442" (miRBase Accession No. MI0016785, SEQ ID NO: 257), which has a hairpin-like structure.
[0130] As used herein, the terms "hsa-miR-1228-3p gene" or "hsa-miR-1228-3p" encompass the hsa-miR-1228-3p gene set forth in SEQ ID NO: 59 (miRBase Accession No. MIMAT0005583) as well as homologs or orthologs from other organisms. The hsa-miR-1228-3p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, vol. 28, pp. 328-336. Furthermore, the precursor of "hsa-miR-1228-3p" is known to be "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 258), which has a hairpin-like structure.
[0131] As used herein, the term "hsa-miR-939-5p gene" or "hsa-miR-939-5p" encompasses the hsa-miR-939-5p gene set forth in SEQ ID NO: 60 (miRBase Accession No. MIMAT0004982) and homologs or orthologs from other organisms. The hsa-miR-939-5p gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, Vol. 67, pp. 6031-6043. Furthermore, the precursor of "hsa-miR-939-5p" is known to be "hsa-mir-939" (miRBase Accession No. MI0005761, SEQ ID NO: 259), which has a hairpin-like structure.
[0132] As used herein, the term "hsa-miR-6845-5p gene" or "hsa-miR-6845-5p" encompasses the hsa-miR-6845-5p gene set forth in SEQ ID NO: 61 (miRBase Accession No. MIMAT0027590) and homologs or orthologs from other organisms. The hsa-miR-6845-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6845-5p" is known to have a precursor, "hsa-mir-6845" (miRBase Accession No. MI0022691, SEQ ID NO: 260), which has a hairpin-like structure.
[0133] As used herein, the term "hsa-miR-887-3p gene" or "hsa-miR-887-3p" encompasses the hsa-miR-887-3p gene set forth in SEQ ID NO: 62 (miRBase Accession No. MIMAT0004951) and homologs or orthologs from other organisms. The hsa-miR-887-3p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, vol. 16, pp. 1289-1298. Furthermore, the precursor of "hsa-miR-887-3p" is known to be "hsa-mir-887" (miRBase Accession No. MI0005562, SEQ ID NO: 261), which has a hairpin-like structure.
[0134] As used herein, the term "hsa-miR-7845-5p gene" or "hsa-miR-7845-5p" encompasses the hsa-miR-7845-5p gene set forth in SEQ ID NO: 63 (miRBase Accession No. MIMAT0030420) and homologs or orthologs from other organisms. The hsa-miR-7845-5p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Furthermore, "hsa-miR-7845-5p" is known to have a precursor, "hsa-mir-7845" (miRBase Accession No. MI0025515, SEQ ID NO: 262), which has a hairpin-like structure.
[0135] As used herein, the term "hsa-miR-6729-5p gene" or "hsa-miR-6729-5p" encompasses the hsa-miR-6729-5p gene set forth in SEQ ID NO: 64 (miRBase Accession No. MIMAT0027359) as well as homologs or orthologs from other organisms. The hsa-miR-6729-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6729-5p" is known to be "hsa-mir-6729" (miRBase Accession No. MI0022574, SEQ ID NO: 263), which has a hairpin-like structure.
[0136] As used herein, the term "hsa-miR-4632-5p gene" or "hsa-miR-4632-5p" encompasses the hsa-miR-4632-5p gene set forth in SEQ ID NO: 65 (miRBase Accession No. MIMAT0022977) as well as homologs or orthologs from other organisms. The hsa-miR-4632-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. It is also known that the precursor of "hsa-miR-4632-5p" is "hsa-mir-4632" (miRBase Accession No. MI0017259, SEQ ID NO: 264), which has a hairpin-like structure.
[0137] As used herein, the term "hsa-miR-615-5p gene" or "hsa-miR-615-5p" encompasses the hsa-miR-615-5p gene set forth in SEQ ID NO: 66 (miRBase Accession No. MIMAT0004804) as well as homologs or orthologs from other organisms. The hsa-miR-615-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103, pp. 3687-3692. Furthermore, the precursor of "hsa-miR-615-5p" is known to be "hsa-mir-615" (miRBase Accession No. MI0003628, SEQ ID NO: 265), which has a hairpin-like structure.
[0138] As used herein, the term "hsa-miR-6724-5p gene" or "hsa-miR-6724-5p" encompasses the hsa-miR-6724-5p gene set forth in SEQ ID NO: 67 (miRBase Accession No. MIMAT0025856) as well as homologs or orthologs from other biological species. The hsa-miR-6724-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, vol. 497, pp. 330-335. Furthermore, the precursor of "hsa-miR-6724-5p" is known to be "hsa-mir-6724" (miRBase Accession No. MI0022559, SEQ ID NO: 266), which has a hairpin-like structure.
[0139] As used herein, the term "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" encompasses the hsa-miR-4728-5p gene set forth in SEQ ID NO: 68 (miRBase Accession No. MIMAT0019849) as well as homologs or orthologs from other organisms. The hsa-miR-4728-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, the precursor of "hsa-miR-4728-5p" is known to be "hsa-mir-4728" (miRBase Accession No. MI0017365, SEQ ID NO: 267), which has a hairpin-like structure.
[0140] As used herein, the term "hsa-miR-6732-5p gene" or "hsa-miR-6732-5p" encompasses the hsa-miR-6732-5p gene set forth in SEQ ID NO: 69 (miRBase Accession No. MIMAT0027365) as well as homologs or orthologs from other organisms. The hsa-miR-6732-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6732-5p" is known to be "hsa-mir-6732" (miRBase Accession No. MI0022577, SEQ ID NO: 268), which has a hairpin-like structure.
[0141] As used herein, the term "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" encompasses the hsa-miR-6816-5p gene set forth in SEQ ID NO: 70 (miRBase Accession No. MIMAT0027532) and homologs or orthologs from other organisms. The hsa-miR-6816-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6816-5p" is known to be "hsa-mir-6816" (miRBase Accession No. MI0022661, SEQ ID NO: 269), which has a hairpin-like structure.
[0142] As used herein, the term "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" encompasses the hsa-miR-4695-5p gene set forth in SEQ ID NO: 71 (miRBase Accession No. MIMAT0019788) as well as homologs or orthologs from other organisms. The hsa-miR-4695-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. It is also known that the precursor of "hsa-miR-4695-5p" is "hsa-mir-4695" (miRBase Accession No. MI0017328, SEQ ID NO: 270), which has a hairpin-like structure.
[0143] As used herein, the term "hsa-miR-6088 gene" or "hsa-miR-6088" encompasses the hsa-miR-6088 gene set forth in SEQ ID NO: 72 (miRBase Accession No. MIMAT0023713) and homologs or orthologs from other organisms. The hsa-miR-6088 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, vol. 21, pp. 2049-2057. Furthermore, "hsa-miR-6088" is known to have a precursor, "hsa-mir-6088" (miRBase Accession No. MI0020365, SEQ ID NO: 271), which has a hairpin-like structure.
[0144] As used herein, the term "hsa-miR-7975 gene" or "hsa-miR-7975" encompasses the hsa-miR-7975 gene set forth in SEQ ID NO: 73 (miRBase Accession No. MIMAT0031178) and homologs or orthologs from other biological species. The hsa-miR-7975 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online edition. Furthermore, "hsa-miR-7975" is known to have a precursor, "hsa-mir-7975" (miRBase Accession No. MI0025751, SEQ ID NO: 272), which has a hairpin-like structure.
[0145] As used herein, the term "hsa-miR-3197 gene" or "hsa-miR-3197" encompasses the hsa-miR-3197 gene set forth in SEQ ID NO: 74 (miRBase Accession No. MIMAT0015082) as well as homologs or orthologs from other organisms. The hsa-miR-3197 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. Furthermore, a known precursor of "hsa-miR-3197" is "hsa-mir-3197" (miRBase Accession No. MI0014245, SEQ ID NO: 273), which has a hairpin-like structure.
[0146] As used herein, the term "hsa-miR-6125 gene" or "hsa-miR-6125" encompasses the hsa-miR-6125 gene set forth in SEQ ID NO: 75 (miRBase Accession No. MIMAT0024598) and homologs or orthologs from other biological species. The hsa-miR-6125 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, vol. 86, pp. 5278-5287. Furthermore, a known precursor of "hsa-miR-6125" is "hsa-mir-6125" (miRBase Accession No. MI0021259, SEQ ID NO: 274), which has a hairpin-like structure.
[0147] As used herein, the term "hsa-miR-4433-3p gene" or "hsa-miR-4433-3p" encompasses the hsa-miR-4433-3p gene set forth in SEQ ID NO: 76 (miRBase Accession No. MIMAT0018949) as well as homologs or orthologs from other species. The hsa-miR-4433-3p gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, the precursor of "hsa-miR-4433-3p" is known to be "hsa-mir-4433" (miRBase Accession No. MI0016773, SEQ ID NO: 275), which has a hairpin-like structure.
[0148] As used herein, the term "hsa-miR-6727-5p gene" or "hsa-miR-6727-5p" encompasses the hsa-miR-6727-5p gene set forth in SEQ ID NO: 77 (miRBase Accession No. MIMAT0027355) as well as homologs or orthologs from other organisms. The hsa-miR-6727-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6727-5p" is known to be "hsa-mir-6727" (miRBase Accession No. MI0022572, SEQ ID NO: 276), which has a hairpin-like structure.
[0149] As used herein, the term "hsa-miR-4706 gene" or "hsa-miR-4706" encompasses the hsa-miR-4706 gene set forth in SEQ ID NO: 78 (miRBase Accession No. MIMAT0019806) as well as homologs or orthologs from other organisms. The hsa-miR-4706 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4706" is "hsa-mir-4706" (miRBase Accession No. MI0017339, SEQ ID NO: 277), which has a hairpin-like structure.
[0150] As used herein, the term "hsa-miR-7847-3p gene" or "hsa-miR-7847-3p" encompasses the hsa-miR-7847-3p gene set forth in SEQ ID NO: 79 (miRBase Accession No. MIMAT0030422) and homologs or orthologs from other organisms. The hsa-miR-7847-3p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Furthermore, the precursor of "hsa-miR-7847-3p" is known to have a hairpin-like structure, "hsa-mir-7847" (miRBase Accession No. MI0025517, SEQ ID NO: 278).
[0151] As used herein, the term "hsa-miR-6805-3p gene" or "hsa-miR-6805-3p" encompasses the hsa-miR-6805-3p gene set forth in SEQ ID NO: 80 (miRBase Accession No. MIMAT0027511) and homologs or orthologs from other organisms. The hsa-miR-6805-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6805-3p" is known to be "hsa-mir-6805" (miRBase Accession No. MI0022650, SEQ ID NO: 279), which has a hairpin-like structure.
[0152] As used herein, the term "hsa-miR-6766-3p gene" or "hsa-miR-6766-3p" encompasses the hsa-miR-6766-3p gene set forth in SEQ ID NO: 81 (miRBase Accession No. MIMAT0027433) as well as homologs or orthologs from other organisms. The hsa-miR-6766-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6766-3p" is known to be "hsa-mir-6766" (miRBase Accession No. MI0022611, SEQ ID NO: 280), which has a hairpin-like structure.
[0153] As used herein, the term "hsa-miR-1913 gene" or "hsa-miR-1913" encompasses the hsa-miR-1913 gene set forth in SEQ ID NO: 82 (miRBase Accession No. MIMAT0007888) as well as homologs or orthologs from other organisms. The hsa-miR-1913 gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, vol. 26, pp. 2496-2505. Furthermore, a known precursor of "hsa-miR-1913" is "hsa-mir-1913" (miRBase Accession No. MI0008334, SEQ ID NO: 281), which has a hairpin-like structure.
[0154] As used herein, the term "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" encompasses the hsa-miR-4649-5p gene set forth in SEQ ID NO: 83 (miRBase Accession No. MIMAT0019711) as well as homologs or orthologs from other organisms. The hsa-miR-4649-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, the precursor of "hsa-miR-4649-5p" is known to be "hsa-mir-4649" (miRBase Accession No. MI0017276, SEQ ID NO: 282), which has a hairpin-like structure.
[0155] As used herein, the term "hsa-miR-602 gene" or "hsa-miR-602" encompasses the hsa-miR-602 gene set forth in SEQ ID NO: 84 (miRBase Accession No. MIMAT0003270) as well as homologs or orthologs from other organisms. The hsa-miR-602 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103, pp. 3687-3692. Furthermore, a known precursor of "hsa-miR-602" is "hsa-mir-602" (miRBase Accession No. MI0003615, SEQ ID NO: 283), which has a hairpin-like structure.
[0156] As used herein, the terms "hsa-miR-3663-3p gene" or "hsa-miR-3663-3p" encompass the hsa-miR-3663-3p gene set forth in SEQ ID NO: 85 (miRBase Accession No. MIMAT0018085) and homologs or orthologs from other organisms. The hsa-miR-3663-3p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. It is also known that the precursor of "hsa-miR-3663-3p" is "hsa-mir-3663" (miRBase Accession No. MI0016064, SEQ ID NO: 284), which has a hairpin-like structure.
[0157] As used herein, the term "hsa-miR-6893-5p gene" or "hsa-miR-6893-5p" encompasses the hsa-miR-6893-5p gene set forth in SEQ ID NO: 86 (miRBase Accession No. MIMAT0027686) as well as homologs or orthologs from other organisms. The hsa-miR-6893-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6893-5p" is known to be "hsa-mir-6893" (miRBase Accession No. MI0022740, SEQ ID NO: 285), which has a hairpin-like structure.
[0158] As used herein, the term "hsa-miR-6861-5p gene" or "hsa-miR-6861-5p" encompasses the hsa-miR-6861-5p gene set forth in SEQ ID NO: 87 (miRBase Accession No. MIMAT0027623) as well as homologs or orthologs from other organisms. The hsa-miR-6861-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6861-5p" is known to be "hsa-mir-6861" (miRBase Accession No. MI0022708, SEQ ID NO: 286), which has a hairpin-like structure.
[0159] As used herein, the term "hsa-miR-4449 gene" or "hsa-miR-4449" encompasses the hsa-miR-4449 gene set forth in SEQ ID NO: 88 (miRBase Accession No. MIMAT0018968) as well as homologs or orthologs from other organisms. The hsa-miR-4449 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4449" is "hsa-mir-4449" (miRBase Accession No. MI0016792, SEQ ID NO: 287), which has a hairpin-like structure.
[0160] As used herein, the term "hsa-miR-6842-5p gene" or "hsa-miR-6842-5p" encompasses the hsa-miR-6842-5p gene set forth in SEQ ID NO: 89 (miRBase Accession No. MIMAT0027586) as well as homologs or orthologs from other organisms. The hsa-miR-6842-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6842-5p" is known to be "hsa-mir-6842" (miRBase Accession No. MI0022688, SEQ ID NO: 288), which has a hairpin-like structure.
[0161] As used herein, the term "hsa-miR-4454 gene" or "hsa-miR-4454" encompasses the hsa-miR-4454 gene set forth in SEQ ID NO: 90 (miRBase Accession No. MIMAT0018976) as well as homologs or orthologs from other organisms. The hsa-miR-4454 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4454" is "hsa-mir-4454" (miRBase Accession No. MI0016800, SEQ ID NO: 289), which has a hairpin-like structure.
[0162] As used herein, the terms "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" encompass the hsa-miR-5195-3p gene set forth in SEQ ID NO: 91 (miRBase Accession No. MIMAT0021127) as well as homologs or orthologs from other organisms. The hsa-miR-5195-3p gene can be obtained by the method described in Schotte D et al., 2011, Leukemia, Vol. 25, pp. 1389-1399. Furthermore, the precursor of "hsa-miR-5195-3p" is known to be "hsa-mir-5195" (miRBase Accession No. MI0018174, SEQ ID NO: 290), which has a hairpin-like structure.
[0163] As used herein, the term "hsa-miR-663b gene" or "hsa-miR-663b" encompasses the hsa-miR-663b gene set forth in SEQ ID NO: 92 (miRBase Accession No. MIMAT0005867) as well as homologs or orthologs from other organisms. The hsa-miR-663b gene can be obtained by the method described in Takada S et al., 2008, Leukemia, Vol. 22, pp. 1274-1278. Furthermore, a known precursor of "hsa-miR-663b" is "hsa-mir-663b" (miRBase Accession No. MI0006336, SEQ ID NO: 291), which has a hairpin-like structure.
[0164] As used herein, the term "hsa-miR-6765-5p gene" or "hsa-miR-6765-5p" encompasses the hsa-miR-6765-5p gene set forth in SEQ ID NO: 93 (miRBase Accession No. MIMAT0027430) as well as homologs or orthologs from other organisms. The hsa-miR-6765-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6765-5p" is known to be "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 292), which has a hairpin-like structure.
[0165] As used herein, the term "hsa-miR-4513 gene" or "hsa-miR-4513" encompasses the hsa-miR-4513 gene set forth in SEQ ID NO: 94 (miRBase Accession No. MIMAT0019050) as well as homologs or orthologs from other biological species. The hsa-miR-4513 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4513" is "hsa-mir-4513" (miRBase Accession No. MI0016879, SEQ ID NO: 293), which has a hairpin-like structure.
[0166] As used herein, the term "hsa-miR-614 gene" or "hsa-miR-614" encompasses the hsa-miR-614 gene set forth in SEQ ID NO: 95 (miRBase Accession No. MIMAT0003282) and homologs or orthologs from other organisms. The hsa-miR-614 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103, pp. 3687-3692. Furthermore, a known precursor of "hsa-miR-614" is "hsa-mir-614" (miRBase Accession No. MI0003627, SEQ ID NO: 294), which has a hairpin-like structure.
[0167] As used herein, the term "hsa-miR-6785-5p gene" or "hsa-miR-6785-5p" encompasses the hsa-miR-6785-5p gene set forth in SEQ ID NO: 96 (miRBase Accession No. MIMAT0027470) as well as homologs or orthologs from other organisms. The hsa-miR-6785-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6785-5p" is known to have a precursor, "hsa-mir-6785" (miRBase Accession No. MI0022630, SEQ ID NO: 295), which has a hairpin-like structure.
[0168] As used herein, the term "hsa-miR-6777-5p gene" or "hsa-miR-6777-5p" encompasses the hsa-miR-6777-5p gene set forth in SEQ ID NO: 97 (miRBase Accession No. MIMAT0027454) as well as homologs or orthologs from other organisms. The hsa-miR-6777-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6777-5p" is known to be "hsa-mir-6777" (miRBase Accession No. MI0022622, SEQ ID NO: 296), which has a hairpin-like structure.
[0169] As used herein, the term "hsa-miR-940 gene" or "hsa-miR-940" encompasses the hsa-miR-940 gene set forth in SEQ ID NO: 98 (miRBase Accession No. MIMAT0004983) as well as homologs or orthologs from other species. The hsa-miR-940 gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, Vol. 67, pp. 6031-6043. Furthermore, "hsa-miR-940" is known to have a precursor, "hsa-mir-940" (miRBase Accession No. MI0005762, SEQ ID NO: 297), which has a hairpin-like structure.
[0170] As used herein, the term "hsa-miR-4741 gene" or "hsa-miR-4741" encompasses the hsa-miR-4741 gene set forth in SEQ ID NO: 99 (miRBase Accession No. MIMAT0019871) as well as homologs or orthologs from other organisms. The hsa-miR-4741 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4741" is "hsa-mir-4741" (miRBase Accession No. MI0017379, SEQ ID NO: 298), which has a hairpin-like structure.
[0171] As used herein, the term "hsa-miR-6870-5p gene" or "hsa-miR-6870-5p" encompasses the hsa-miR-6870-5p gene set forth in SEQ ID NO: 100 (miRBase Accession No. MIMAT0027640) and homologs or orthologs from other organisms. The hsa-miR-6870-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6870-5p" is known to have a precursor, "hsa-mir-6870" (miRBase Accession No. MI0022717, SEQ ID NO: 299), which has a hairpin-like structure.
[0172] As used herein, the term "hsa-miR-6131 gene" or "hsa-miR-6131" encompasses the hsa-miR-6131 gene set forth in SEQ ID NO: 101 (miRBase Accession No. MIMAT0024615) as well as homologs or orthologs from other organisms. The hsa-miR-6131 gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol, vol. 4, pp. 552-564. Furthermore, "hsa-miR-6131" is known to have a precursor, "hsa-mir-6131" (miRBase Accession No. MI0021276, SEQ ID NO: 300), which has a hairpin-like structure.
[0173] As used herein, the terms "hsa-miR-150-3p gene" or "hsa-miR-150-3p" encompass the hsa-miR-150-3p gene set forth in SEQ ID NO: 102 (miRBase Accession No. MIMAT0004610) and homologs or orthologs from other organisms. The hsa-miR-150-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, vol. 12, pp. 735-739. Furthermore, the precursor of "hsa-miR-150-3p" is known to be "hsa-mir-150" (miRBase Accession No. MI0000479, SEQ ID NO: 301), which has a hairpin-like structure.
[0174] As used herein, the term "hsa-miR-4707-5p gene" or "hsa-miR-4707-5p" encompasses the hsa-miR-4707-5p gene set forth in SEQ ID NO: 103 (miRBase Accession No. MIMAT0019807) as well as homologs or orthologs from other organisms. The hsa-miR-4707-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, the precursor of "hsa-miR-4707-5p" is known to be "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 302), which has a hairpin-like structure.
[0175] As used herein, the term "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" encompasses the hsa-miR-1915-3p gene set forth in SEQ ID NO: 104 (miRBase Accession No. MIMAT0007892) as well as homologs or orthologs from other organisms. The hsa-miR-1915-3p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, vol. 26, pp. 2496-2505. It is also known that the precursor of "hsa-miR-1915-3p" is "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 303), which has a hairpin-like structure.
[0176] As used herein, the term "hsa-miR-3937 gene" or "hsa-miR-3937" encompasses the hsa-miR-3937 gene set forth in SEQ ID NO: 105 (miRBase Accession No. MIMAT0018352) and homologs or orthologs from other species. The hsa-miR-3937 gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Furthermore, a known precursor of "hsa-miR-3937" is "hsa-mir-3937" (miRBase Accession No. MI0016593, SEQ ID NO: 304), which has a hairpin-like structure.
[0177] As used herein, the term "hsa-miR-937-5p gene" or "hsa-miR-937-5p" encompasses the hsa-miR-937-5p gene set forth in SEQ ID NO: 106 (miRBase Accession No. MIMAT0022938) as well as homologs or orthologs from other organisms. The hsa-miR-937-5p gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, vol. 67, pp. 6031-6043. Furthermore, the precursor of "hsa-miR-937-5p" is known to be "hsa-mir-937" (miRBase Accession No. MI0005759, SEQ ID NO: 305), which has a hairpin-like structure.
[0178] As used herein, the term "hsa-miR-4443 gene" or "hsa-miR-4443" encompasses the hsa-miR-4443 gene set forth in SEQ ID NO: 107 (miRBase Accession No. MIMAT0018961) and homologs or orthologs from other biological species. The hsa-miR-4443 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4443" is "hsa-mir-4443" (miRBase Accession No. MI0016786, SEQ ID NO: 306), which has a hairpin-like structure.
[0179] As used herein, the term "hsa-miR-1914-3p gene" or "hsa-miR-1914-3p" encompasses the hsa-miR-1914-3p gene set forth in SEQ ID NO: 108 (miRBase Accession No. MIMAT0007890) as well as homologs or orthologs from other organisms. The hsa-miR-1914-3p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, vol. 26, pp. 2496-2505. It is also known that the precursor of "hsa-miR-1914-3p" is "hsa-mir-1914" (miRBase Accession No. MI0008335, SEQ ID NO: 307), which has a hairpin-like structure.
[0180] As used herein, the terms "hsa-miR-3620-5p gene" or "hsa-miR-3620-5p" encompass the hsa-miR-3620-5p gene set forth in SEQ ID NO: 109 (miRBase Accession No. MIMAT0022967) as well as homologs or orthologs from other organisms. The hsa-miR-3620-5p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, vol. 8, p. 58. It is also known that the precursor of "hsa-miR-3620-5p" is "hsa-mir-3620" (miRBase Accession No. MI0016011, SEQ ID NO: 308), which has a hairpin-like structure.
[0181] As used herein, the term "hsa-miR-1268b gene" or "hsa-miR-1268b" encompasses the hsa-miR-1268b gene set forth in SEQ ID NO: 110 (miRBase Accession No. MIMAT0018925) as well as homologs or orthologs from other species. The hsa-miR-1268b gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, "hsa-miR-1268b" is known to have a precursor, "hsa-mir-1268b" (miRBase Accession No. MI0016748, SEQ ID NO: 309), which has a hairpin-like structure.
[0182] As used herein, the term "hsa-miR-1227-5p gene" or "hsa-miR-1227-5p" encompasses the hsa-miR-1227-5p gene set forth in SEQ ID NO: 111 (miRBase Accession No. MIMAT0022941) and homologs or orthologs from other organisms. The hsa-miR-1227-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, vol. 28, pp. 328-336. Furthermore, the precursor of "hsa-miR-1227-5p" is known to be "hsa-mir-1227" (miRBase Accession No. MI0006316, SEQ ID NO: 310), which has a hairpin-like structure.
[0183] As used herein, the term "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" encompasses the hsa-miR-6880-5p gene set forth in SEQ ID NO: 112 (miRBase Accession No. MIMAT0027660) and homologs or orthologs from other organisms. The hsa-miR-6880-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6880-5p" is known to be "hsa-mir-6880" (miRBase Accession No. MI0022727, SEQ ID NO: 311), which has a hairpin-like structure.
[0184] As used herein, the term "hsa-miR-4417 gene" or "hsa-miR-4417" encompasses the hsa-miR-4417 gene set forth in SEQ ID NO: 113 (miRBase Accession No. MIMAT0018929) as well as homologs or orthologs from other species. The hsa-miR-4417 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4417" is "hsa-mir-4417" (miRBase Accession No. MI0016753, SEQ ID NO: 312), which has a hairpin-like structure.
[0185] As used herein, the term "hsa-miR-6802-5p gene" or "hsa-miR-6802-5p" encompasses the hsa-miR-6802-5p gene set forth in SEQ ID NO: 114 (miRBase Accession No. MIMAT0027504) and homologs or orthologs from other organisms. The hsa-miR-6802-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6802-5p" is known to be "hsa-mir-6802" (miRBase Accession No. MI0022647, SEQ ID NO: 313), which has a hairpin-like structure.
[0186] As used herein, the term "hsa-miR-6769a-5p gene" or "hsa-miR-6769a-5p" encompasses the hsa-miR-6769a-5p gene set forth in SEQ ID NO: 115 (miRBase Accession No. MIMAT0027438) and homologs or orthologs from other organisms. The hsa-miR-6769a-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6769a-5p" is known to be "hsa-mir-6769a" (miRBase Accession No. MI0022614, SEQ ID NO: 314), which has a hairpin-like structure.
[0187] As used herein, the term "hsa-miR-663a gene" or "hsa-miR-663a" encompasses the hsa-miR-663a gene set forth in SEQ ID NO: 116 (miRBase Accession No. MIMAT0003326) and homologs or orthologs from other organisms. The hsa-miR-663a gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103, pp. 3687-3692. Furthermore, "hsa-miR-663a" is known to have a precursor, "hsa-mir-663a" (miRBase Accession No. MI0003672, SEQ ID NO: 315), which has a hairpin-like structure.
[0188] As used herein, the term "hsa-miR-6721-5p gene" or "hsa-miR-6721-5p" encompasses the hsa-miR-6721-5p gene set forth in SEQ ID NO: 117 (miRBase Accession No. MIMAT0025852) as well as homologs or orthologs from other organisms. The hsa-miR-6721-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, vol. 497, pp. 330-335. Furthermore, the precursor of "hsa-miR-6721-5p" is known to be "hsa-mir-6721" (miRBase Accession No. MI0022556, SEQ ID NO: 316), which has a hairpin-like structure.
[0189] As used herein, the term "hsa-miR-4532 gene" or "hsa-miR-4532" encompasses the hsa-miR-4532 gene set forth in SEQ ID NO: 118 (miRBase Accession No. MIMAT0019071) and homologs or orthologs from other organisms. The hsa-miR-4532 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4532" is "hsa-mir-4532" (miRBase Accession No. MI0016899, SEQ ID NO: 317), which has a hairpin-like structure.
[0190] As used herein, the term "hsa-miR-7977 gene" or "hsa-miR-7977" encompasses the hsa-miR-7977 gene set forth in SEQ ID NO: 119 (miRBase Accession No. MIMAT0031180) as well as homologs or orthologs from other species. The hsa-miR-7977 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online edition. Furthermore, a known precursor of "hsa-miR-7977" is "hsa-mir-7977" (miRBase Accession No. MI0025753, SEQ ID NO: 318), which has a hairpin-like structure.
[0191] As used herein, the term "hsa-miR-92b-5p gene" or "hsa-miR-92b-5p" encompasses the hsa-miR-92b-5p gene set forth in SEQ ID NO: 120 (miRBase Accession No. MIMAT0004792) and homologs or orthologs from other organisms. The hsa-miR-92b-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103, pp. 3687-3692. Furthermore, the precursor of "hsa-miR-92b-5p" is known to be "hsa-mir-92b" (miRBase Accession No. MI0003560, SEQ ID NO: 319), which has a hairpin-like structure.
[0192] As used herein, the term "hsa-miR-371a-5p gene" or "hsa-miR-371a-5p" encompasses the hsa-miR-371a-5p gene set forth in SEQ ID NO: 121 (miRBase Accession No. MIMAT0004687) and homologs or orthologs from other organisms. The hsa-miR-371a-5p gene can be obtained by the method described in Suh MR et al., 2004, Dev Biol, vol. 270, pp. 488-498. It is also known that the precursor of "hsa-miR-371a-5p" is "hsa-mir-371a" (miRBase Accession No. MI0000779, SEQ ID NO: 320), which has a hairpin-like structure.
[0193] As used herein, the term "hsa-miR-6126 gene" or "hsa-miR-6126" encompasses the hsa-miR-6126 gene set forth in SEQ ID NO: 122 (miRBase Accession No. MIMAT0024599) as well as homologs or orthologs from other organisms. The hsa-miR-6126 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, vol. 86, pp. 5278-5287. Furthermore, a known precursor of "hsa-miR-6126" is "hsa-mir-6126" (miRBase Accession No. MI0021260, SEQ ID NO: 321), which has a hairpin-like structure.
[0194] As used herein, the term "hsa-miR-4734 gene" or "hsa-miR-4734" encompasses the hsa-miR-4734 gene set forth in SEQ ID NO: 123 (miRBase Accession No. MIMAT0019859) as well as homologs or orthologs from other organisms. The hsa-miR-4734 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4734" is "hsa-mir-4734" (miRBase Accession No. MI0017371, SEQ ID NO: 322), which has a hairpin-like structure.
[0195] As used herein, the term "hsa-miR-4665-3p gene" or "hsa-miR-4665-3p" encompasses the hsa-miR-4665-3p gene set forth in SEQ ID NO: 124 (miRBase Accession No. MIMAT0019740) as well as homologs or orthologs from other organisms. The hsa-miR-4665-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, the precursor of "hsa-miR-4665-3p" is known to be "hsa-mir-4665" (miRBase Accession No. MI0017295, SEQ ID NO: 323), which has a hairpin-like structure.
[0196] As used herein, the terms "hsa-miR-423-5p gene" or "hsa-miR-423-5p" encompass the hsa-miR-423-5p gene set forth in SEQ ID NO: 125 (miRBase Accession No. MIMAT0004748) as well as homologs or orthologs from other organisms. The hsa-miR-423-5p gene can be obtained by the method described in Kasashima K et al., 2004, Biochem Biophys Res Commun, vol. 322, pp. 403-410. Furthermore, the precursor of "hsa-miR-423-5p" is known to be "hsa-mir-423" (miRBase Accession No. MI0001445, SEQ ID NO: 324), which has a hairpin-like structure.
[0197] As used herein, the term "hsa-miR-1469 gene" or "hsa-miR-1469" encompasses the hsa-miR-1469 gene set forth in SEQ ID NO: 126 (miRBase Accession No. MIMAT0007347) as well as homologs or orthologs from other organisms. The hsa-miR-1469 gene can be obtained by the method described in Kawaji H et al., 2008, BMC Genomics, Vol. 9, p. 157. Furthermore, "hsa-miR-1469" is known to have a precursor, "hsa-mir-1469" (miRBase Accession No. MI0007074, SEQ ID NO: 325), which has a hairpin-like structure.
[0198] As used herein, the term "hsa-miR-4675 gene" or "hsa-miR-4675" encompasses the hsa-miR-4675 gene set forth in SEQ ID NO: 127 (miRBase Accession No. MIMAT0019757) as well as homologs or orthologs from other organisms. The hsa-miR-4675 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4675" is "hsa-mir-4675" (miRBase Accession No. MI0017306, SEQ ID NO: 326), which has a hairpin-like structure.
[0199] As used herein, the terms "hsa-miR-1915-5p gene" or "hsa-miR-1915-5p" encompass the hsa-miR-1915-5p gene set forth in SEQ ID NO: 128 (miRBase Accession No. MIMAT0007891) and homologs or orthologs from other organisms. The hsa-miR-1915-5p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, vol. 26, pp. 2496-2505. It is also known that the precursor of "hsa-miR-1915-5p" is "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 303), which has a hairpin-like structure.
[0200] As used herein, the term "hsa-miR-6716-5p gene" or "hsa-miR-6716-5p" encompasses the hsa-miR-6716-5p gene set forth in SEQ ID NO: 129 (miRBase Accession No. MIMAT0025844) and homologs or orthologs from other biological species. The hsa-miR-6716-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, vol. 497, pp. 330-335. It is also known that the precursor of "hsa-miR-6716-5p" is "hsa-mir-6716" (miRBase Accession No. MI0022550, SEQ ID NO: 327), which has a hairpin-like structure.
[0201] As used herein, the term "hsa-miR-718 gene" or "hsa-miR-718" encompasses the hsa-miR-718 gene set forth in SEQ ID NO: 130 (miRBase Accession No. MIMAT0012735) as well as homologs or orthologs from other species. The hsa-miR-718 gene can be obtained by the method described in Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p. 39. Furthermore, "hsa-miR-718" is known to have a precursor, "hsa-mir-718" (miRBase Accession No. MI0012489, SEQ ID NO: 328), which has a hairpin-like structure.
[0202] As used herein, the term "hsa-miR-4281 gene" or "hsa-miR-4281" encompasses the hsa-miR-4281 gene set forth in SEQ ID NO: 131 (miRBase Accession No. MIMAT0016907) as well as homologs or orthologs from other organisms. The hsa-miR-4281 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, vol. 4, e7192. Furthermore, "hsa-miR-4281" is known to have a precursor, "hsa-mir-4281" (miRBase Accession No. MI0015885, SEQ ID NO: 329), which has a hairpin-like structure.
[0203] As used herein, the term "hsa-miR-6820-5p gene" or "hsa-miR-6820-5p" encompasses the hsa-miR-6820-5p gene set forth in SEQ ID NO: 132 (miRBase Accession No. MIMAT0027540) and homologs or orthologs from other organisms. The hsa-miR-6820-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6820-5p" is known to be "hsa-mir-6820" (miRBase Accession No. MI0022665, SEQ ID NO: 330), which has a hairpin-like structure.
[0204] As used herein, the term "hsa-miR-6795-5p gene" or "hsa-miR-6795-5p" encompasses the hsa-miR-6795-5p gene set forth in SEQ ID NO: 133 (miRBase Accession No. MIMAT0027490) and homologs or orthologs from other organisms. The hsa-miR-6795-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6795-5p" is known to have a precursor, "hsa-mir-6795" (miRBase Accession No. MI0022640, SEQ ID NO: 331), which has a hairpin-like structure.
[0205] As used herein, the term "hsa-miR-6779-5p gene" or "hsa-miR-6779-5p" encompasses the hsa-miR-6779-5p gene set forth in SEQ ID NO: 134 (miRBase Accession No. MIMAT0027458) as well as homologs or orthologs from other organisms. The hsa-miR-6779-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6779-5p" is known to be "hsa-mir-6779" (miRBase Accession No. MI0022624, SEQ ID NO: 332), which has a hairpin-like structure.
[0206] As used herein, the term "hsa-miR-7109-5p gene" or "hsa-miR-7109-5p" encompasses the hsa-miR-7109-5p gene set forth in SEQ ID NO: 135 (miRBase Accession No. MIMAT0028115) and homologs or orthologs from other organisms. The hsa-miR-7109-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-7109-5p" is known to have a precursor, "hsa-mir-7109" (miRBase Accession No. MI0022960, SEQ ID NO: 333), which has a hairpin-like structure.
[0207] As used herein, the term "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" encompasses the hsa-miR-6798-5p gene set forth in SEQ ID NO: 136 (miRBase Accession No. MIMAT0027496) and homologs or orthologs from other organisms. The hsa-miR-6798-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6798-5p" is known to be "hsa-mir-6798" (miRBase Accession No. MI0022643, SEQ ID NO: 334), which has a hairpin-like structure.
[0208] As used herein, the term "hsa-miR-4648 gene" or "hsa-miR-4648" encompasses the hsa-miR-4648 gene set forth in SEQ ID NO: 137 (miRBase Accession No. MIMAT0019710) as well as homologs or orthologs from other organisms. The hsa-miR-4648 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4648" is "hsa-mir-4648" (miRBase Accession No. MI0017275, SEQ ID NO: 335), which has a hairpin-like structure.
[0209] As used herein, the term "hsa-miR-8059 gene" or "hsa-miR-8059" encompasses the hsa-miR-8059 gene set forth in SEQ ID NO: 138 (miRBase Accession No. MIMAT0030986) and homologs or orthologs from other organisms. The hsa-miR-8059 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, vol. 39, pp. 480-487. Furthermore, "hsa-miR-8059" is known to have a precursor, "hsa-mir-8059" (miRBase Accession No. MI0025895, SEQ ID NO: 336), which has a hairpin-like structure.
[0210] As used herein, the term "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" encompasses the hsa-miR-6765-3p gene set forth in SEQ ID NO: 139 (miRBase Accession No. MIMAT0027431) and homologs or orthologs from other organisms. The hsa-miR-6765-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6765-3p" is known to be "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 292), which has a hairpin-like structure.
[0211] As used herein, the term "hsa-miR-6132 gene" or "hsa-miR-6132" encompasses the hsa-miR-6132 gene set forth in SEQ ID NO: 140 (miRBase Accession No. MIMAT0024616) as well as homologs or orthologs from other species. The hsa-miR-6132 gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol, vol. 4, pp. 552-564. Furthermore, a known precursor of "hsa-miR-6132" is "hsa-mir-6132" (miRBase Accession No. MI0021277, SEQ ID NO: 337), which has a hairpin-like structure.
[0212] As used herein, the term "hsa-miR-4492 gene" or "hsa-miR-4492" encompasses the hsa-miR-4492 gene set forth in SEQ ID NO: 141 (miRBase Accession No. MIMAT0019027) as well as homologs or orthologs from other species. The hsa-miR-4492 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4492" is "hsa-mir-4492" (miRBase Accession No. MI0016854, SEQ ID NO: 338), which has a hairpin-like structure.
[0213] As used herein, the term "hsa-miR-7107-5p gene" or "hsa-miR-7107-5p" encompasses the hsa-miR-7107-5p gene set forth in SEQ ID NO: 142 (miRBase Accession No. MIMAT0028111) and homologs or orthologs from other organisms. The hsa-miR-7107-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-7107-5p" is known to be "hsa-mir-7107" (miRBase Accession No. MI0022958, SEQ ID NO: 339), which has a hairpin-like structure.
[0214] As used herein, the term "hsa-miR-3195 gene" or "hsa-miR-3195" encompasses the hsa-miR-3195 gene set forth in SEQ ID NO: 143 (miRBase Accession No. MIMAT0015079) as well as homologs or orthologs from other organisms. The hsa-miR-3195 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. Furthermore, "hsa-miR-3195" is known to have a precursor, "hsa-mir-3195" (miRBase Accession No. MI0014240, SEQ ID NO: 340), which has a hairpin-like structure.
[0215] As used herein, the term "hsa-miR-3180 gene" or "hsa-miR-3180" encompasses the hsa-miR-3180 gene set forth in SEQ ID NO: 144 (miRBase Accession No. MIMAT0018178) as well as homologs or orthologs from other species. The hsa-miR-3180 gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, vol. 5, e9637. Furthermore, "hsa-miR-3180" is known to have precursors with hairpin-like structures, such as "hsa-mir-3180-4" and "hsa-mir-3180-5" (miRBase Accession Nos. MI0016408 and MI0016409, SEQ ID NOs: 341 and 342).
[0216] As used herein, the term "hsa-miR-296-3p gene" or "hsa-miR-296-3p" encompasses the hsa-miR-296-3p gene set forth in SEQ ID NO: 145 (miRBase Accession No. MIMAT0004679) as well as homologs or orthologs from other organisms. The hsa-miR-296-3p gene can be obtained by the method described in Houbaviy HB et al., 2003, Dev Cell, vol. 5, pp. 351-358. It is also known that the precursor of "hsa-miR-296-3p" is "hsa-mir-296" (miRBase Accession No. MI0000747, SEQ ID NO: 343), which has a hairpin-like structure.
[0217] As used herein, the term "hsa-miR-564 gene" or "hsa-miR-564" encompasses the hsa-miR-564 gene set forth in SEQ ID NO: 146 (miRBase Accession No. MIMAT0003228) as well as homologs or orthologs from other organisms. The hsa-miR-564 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103, pp. 3687-3692. Furthermore, a known precursor of "hsa-miR-564" is "hsa-mir-564" (miRBase Accession No. MI0003570, SEQ ID NO: 344), which has a hairpin-like structure.
[0218] As used herein, the term "hsa-miR-1268a gene" or "hsa-miR-1268a" encompasses the hsa-miR-1268a gene set forth in SEQ ID NO: 147 (miRBase Accession No. MIMAT0005922) and homologs or orthologs from other organisms. The hsa-miR-1268a gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, vol. 18, pp. 610-621. Furthermore, "hsa-miR-1268a" is known to have a precursor, "hsa-mir-1268a" (miRBase Accession No. MI0006405, SEQ ID NO: 345), which has a hairpin-like structure.
[0219] As used herein, the term "hsa-miR-6848-5p gene" or "hsa-miR-6848-5p" encompasses the hsa-miR-6848-5p gene set forth in SEQ ID NO: 148 (miRBase Accession No. MIMAT0027596) and homologs or orthologs from other organisms. The hsa-miR-6848-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6848-5p" is known to be "hsa-mir-6848" (miRBase Accession No. MI0022694, SEQ ID NO: 346), which has a hairpin-like structure.
[0220] As used herein, the term "hsa-miR-762 gene" or "hsa-miR-762" encompasses the hsa-miR-762 gene set forth in SEQ ID NO: 149 (miRBase Accession No. MIMAT0010313) as well as homologs or orthologs from other organisms. The hsa-miR-762 gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, vol. 16, pp. 1289-1298. Furthermore, a known precursor of "hsa-miR-762" is "hsa-mir-762" (miRBase Accession No. MI0003892, SEQ ID NO: 347), which has a hairpin-like structure.
[0221] As used herein, the term "hsa-miR-2861 gene" or "hsa-miR-2861" encompasses the hsa-miR-2861 gene set forth in SEQ ID NO: 150 (miRBase Accession No. MIMAT0013802) and homologs or orthologs from other organisms. The hsa-miR-2861 gene can be obtained by the method described in Li H et al., 2009, J Clin Invest, vol. 119, pp. 3666-3677. Furthermore, "hsa-miR-2861" is known to have a precursor, "hsa-mir-2861" (miRBase Accession No. MI0013006, SEQ ID NO: 348), which has a hairpin-like structure.
[0222] As used herein, the term "hsa-miR-1203 gene" or "hsa-miR-1203" encompasses the hsa-miR-1203 gene set forth in SEQ ID NO: 151 (miRBase Accession No. MIMAT0005866) as well as homologs or orthologs from other organisms. The hsa-miR-1203 gene can be obtained by the method described in Marton S et al., 2008, Leukemia, vol. 22, pp. 330-338. Furthermore, a known precursor of "hsa-miR-1203" is "hsa-mir-1203" (miRBase Accession No. MI0006335, SEQ ID NO: 349), which has a hairpin-like structure.
[0223] As used herein, the term "hsa-miR-1260b gene" or "hsa-miR-1260b" encompasses the hsa-miR-1260b gene set forth in SEQ ID NO: 152 (miRBase Accession No. MIMAT0015041) as well as homologs or orthologs from other organisms. The hsa-miR-1260b gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. Furthermore, a known precursor of "hsa-miR-1260b" is "hsa-mir-1260b" (miRBase Accession No. MI0014197, SEQ ID NO: 350), which has a hairpin-like structure.
[0224] As used herein, the term "hsa-miR-4476 gene" or "hsa-miR-4476" encompasses the hsa-miR-4476 gene set forth in SEQ ID NO: 153 (miRBase Accession No. MIMAT0019003) and homologs or orthologs from other organisms. The hsa-miR-4476 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4476" is "hsa-mir-4476" (miRBase Accession No. MI0016828, SEQ ID NO: 351), which has a hairpin-like structure.
[0225] As used herein, the term "hsa-miR-6885-5p gene" or "hsa-miR-6885-5p" encompasses the hsa-miR-6885-5p gene set forth in SEQ ID NO: 154 (miRBase Accession No. MIMAT0027670) and homologs or orthologs from other organisms. The hsa-miR-6885-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6885-5p" is known to be "hsa-mir-6885" (miRBase Accession No. MI0022732, SEQ ID NO: 352), which has a hairpin-like structure.
[0226] As used herein, the term "hsa-miR-6769b-5p gene" or "hsa-miR-6769b-5p" encompasses the hsa-miR-6769b-5p gene set forth in SEQ ID NO: 155 (miRBase Accession No. MIMAT0027620) and homologs or orthologs from other organisms. The hsa-miR-6769b-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6769b-5p" is known to be "hsa-mir-6769b" (miRBase Accession No. MI0022706, SEQ ID NO: 353), which has a hairpin-like structure.
[0227] As used herein, the term "hsa-miR-23b-3p gene" or "hsa-miR-23b-3p" encompasses the hsa-miR-23b-3p gene set forth in SEQ ID NO: 156 (miRBase Accession No. MIMAT0000418) and homologs or orthologs from other organisms. The hsa-miR-23b-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, vol. 12, pp. 735-739. Furthermore, the precursor of "hsa-miR-23b-3p" is known to be "hsa-mir-23b" (miRBase Accession No. MI0000439, SEQ ID NO: 354), which has a hairpin-like structure.
[0228] As used herein, the term "hsa-miR-1343-5p gene" or "hsa-miR-1343-5p" encompasses the hsa-miR-1343-5p gene set forth in SEQ ID NO: 157 (miRBase Accession No. MIMAT0027038) as well as homologs or orthologs from other organisms. The hsa-miR-1343-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. It is also known that the precursor of "hsa-miR-1343-5p" is "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 202), which has a hairpin-like structure.
[0229] As used herein, the term "hsa-miR-3621 gene" or "hsa-miR-3621" encompasses the hsa-miR-3621 gene set forth in SEQ ID NO: 158 (miRBase Accession No. MIMAT0018002) and homologs or orthologs from other organisms. The hsa-miR-3621 gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, vol. 8, p. 58. Furthermore, a known precursor of "hsa-miR-3621" is "hsa-mir-3621" (miRBase Accession No. MI0016012, SEQ ID NO: 355), which has a hairpin-like structure.
[0230] As used herein, the term "hsa-miR-4688 gene" or "hsa-miR-4688" encompasses the hsa-miR-4688 gene set forth in SEQ ID NO: 159 (miRBase Accession No. MIMAT0019777) as well as homologs or orthologs from other organisms. The hsa-miR-4688 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4688" is "hsa-mir-4688" (miRBase Accession No. MI0017321, SEQ ID NO: 356), which has a hairpin-like structure.
[0231] As used herein, the term "hsa-miR-4286 gene" or "hsa-miR-4286" encompasses the hsa-miR-4286 gene set forth in SEQ ID NO: 160 (miRBase Accession No. MIMAT0016916) as well as homologs or orthologs from other organisms. The hsa-miR-4286 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, vol. 4, e7192. Furthermore, a known precursor of "hsa-miR-4286" is "hsa-mir-4286" (miRBase Accession No. MI0015894, SEQ ID NO: 357), which has a hairpin-like structure.
[0232] As used herein, the terms "hsa-miR-4640-5p gene" or "hsa-miR-4640-5p" encompass the hsa-miR-4640-5p gene set forth in SEQ ID NO: 161 (miRBase Accession No. MIMAT0019699) as well as homologs or orthologs from other organisms. The hsa-miR-4640-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, the precursor of "hsa-miR-4640-5p" is known to be "hsa-mir-4640" (miRBase Accession No. MI0017267, SEQ ID NO: 358), which has a hairpin-like structure.
[0233] As used herein, the term "hsa-miR-4739 gene" or "hsa-miR-4739" encompasses the hsa-miR-4739 gene set forth in SEQ ID NO: 162 (miRBase Accession No. MIMAT0019868) as well as homologs or orthologs from other organisms. The hsa-miR-4739 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4739" is "hsa-mir-4739" (miRBase Accession No. MI0017377, SEQ ID NO: 359), which has a hairpin-like structure.
[0234] As used herein, the term "hsa-miR-1260a gene" or "hsa-miR-1260a" encompasses the hsa-miR-1260a gene set forth in SEQ ID NO: 163 (miRBase Accession No. MIMAT0005911) and homologs or orthologs from other organisms. The hsa-miR-1260a gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, vol. 18, pp. 610-621. Furthermore, "hsa-miR-1260a" is known to have a precursor, "hsa-mir-1260a" (miRBase Accession No. MI0006394, SEQ ID NO: 360), which has a hairpin-like structure.
[0235] As used herein, the term "hsa-miR-4276 gene" or "hsa-miR-4276" encompasses the hsa-miR-4276 gene set forth in SEQ ID NO: 164 (miRBase Accession No. MIMAT0016904) as well as homologs or orthologs from other organisms. The hsa-miR-4276 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, vol. 4, e7192. Furthermore, a known precursor of "hsa-miR-4276" is "hsa-mir-4276" (miRBase Accession No. MI0015882, SEQ ID NO: 361), which has a hairpin-like structure.
[0236] As used herein, the term "hsa-miR-7106-5p gene" or "hsa-miR-7106-5p" encompasses the hsa-miR-7106-5p gene set forth in SEQ ID NO: 165 (miRBase Accession No. MIMAT0028109) and homologs or orthologs from other organisms. The hsa-miR-7106-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-7106-5p" is known to be "hsa-mir-7106" (miRBase Accession No. MI0022957, SEQ ID NO: 362), which has a hairpin-like structure.
[0237] As used herein, the term "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" encompasses the hsa-miR-128-2-5p gene set forth in SEQ ID NO: 166 (miRBase Accession No. MIMAT0031095) and homologs or orthologs from other species. The hsa-miR-128-2-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, vol. 12, pp. 735-739. Furthermore, the precursor of "hsa-miR-128-2-5p" is known to be "hsa-mir-128-2" (miRBase Accession No. MI0000727, SEQ ID NO: 363), which has a hairpin-like structure.
[0238] As used herein, the term "hsa-miR-125a-3p gene" or "hsa-miR-125a-3p" encompasses the hsa-miR-125a-3p gene set forth in SEQ ID NO: 167 (miRBase Accession No. MIMAT0004602) and homologs or orthologs from other organisms. The hsa-miR-125a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, vol. 12, pp. 735-739. Furthermore, the precursor of "hsa-miR-125a-3p" is known to be "hsa-mir-125a" (miRBase Accession No. MI0000469, SEQ ID NO: 364), which has a hairpin-like structure.
[0239] As used herein, the term "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" encompasses the hsa-miR-92a-2-5p gene set forth in SEQ ID NO: 168 (miRBase Accession No. MIMAT0004508) and homologs or orthologs from other species. The hsa-miR-92a-2-5p gene can be obtained by the method described in Mourelatos Z et al., 2002, Genes Dev, vol. 16, pp. 720-728. Furthermore, the precursor of "hsa-miR-92a-2-5p" is known to be "hsa-mir-92a-2" (miRBase Accession No. MI0000094, SEQ ID NO: 365), which has a hairpin-like structure.
[0240] As used herein, the terms "hsa-miR-486-3p gene" or "hsa-miR-486-3p" encompass the hsa-miR-486-3p gene set forth in SEQ ID NO: 169 (miRBase Accession No. MIMAT0004762) as well as homologs or orthologs from other organisms. The hsa-miR-486-3p gene can be obtained by the method described in Fu H et al., 2005, FEBS Lett., vol. 579, pp. 3849-3854. Furthermore, "hsa-miR-486-3p" is known to have precursors with hairpin-like structures, such as "hsa-mir-486, hsa-mir-486-2" (miRBase Accession Nos. MI0002470, MI0023622, SEQ ID NOs: 366, 367).
[0241] As used herein, the term "hsa-miR-3196 gene" or "hsa-miR-3196" encompasses the hsa-miR-3196 gene set forth in SEQ ID NO: 170 (miRBase Accession No. MIMAT0015080) as well as homologs or orthologs from other organisms. The hsa-miR-3196 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. Furthermore, a known precursor of "hsa-miR-3196" is "hsa-mir-3196" (miRBase Accession No. MI0014241, SEQ ID NO: 368), which has a hairpin-like structure.
[0242] As used herein, the term "hsa-miR-211-3p gene" or "hsa-miR-211-3p" encompasses the hsa-miR-211-3p gene set forth in SEQ ID NO: 171 (miRBase Accession No. MIMAT0022694) as well as homologs or orthologs from other organisms. The hsa-miR-211-3p gene can be obtained by the method described in Lim LP et al., 2003, Science, vol. 299, p. 1540. It is also known that the precursor of "hsa-miR-211-3p" is "hsa-mir-211" (miRBase Accession No. MI0000287, SEQ ID NO: 369), which has a hairpin-like structure.
[0243] As used herein, the term "hsa-miR-4271 gene" or "hsa-miR-4271" encompasses the hsa-miR-4271 gene set forth in SEQ ID NO: 172 (miRBase Accession No. MIMAT0016901) as well as homologs or orthologs from other organisms. The hsa-miR-4271 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, vol. 4, e7192. Furthermore, "hsa-miR-4271" is known to have a precursor, "hsa-mir-4271" (miRBase Accession No. MI0015879, SEQ ID NO: 370), which has a hairpin-like structure.
[0244] As used herein, the term "hsa-miR-6851-5p gene" or "hsa-miR-6851-5p" encompasses the hsa-miR-6851-5p gene set forth in SEQ ID NO: 173 (miRBase Accession No. MIMAT0027602) and homologs or orthologs from other organisms. The hsa-miR-6851-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6851-5p" is known to be "hsa-mir-6851" (miRBase Accession No. MI0022697, SEQ ID NO: 371), which has a hairpin-like structure.
[0245] As used herein, the terms "hsa-miR-149-3p gene" or "hsa-miR-149-3p" encompass the hsa-miR-149-3p gene set forth in SEQ ID NO: 174 (miRBase Accession No. MIMAT0004609) as well as homologs or orthologs from other organisms. The hsa-miR-149-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, vol. 12, pp. 735-739. Furthermore, "hsa-miR-149-3p" is known to have a precursor, "hsa-mir-149" (miRBase Accession No. MI0000478, SEQ ID NO: 372), which has a hairpin-like structure.
[0246] As used herein, the term "hsa-miR-4667-5p gene" or "hsa-miR-4667-5p" encompasses the hsa-miR-4667-5p gene set forth in SEQ ID NO: 175 (miRBase Accession No. MIMAT0019743) as well as homologs or orthologs from other organisms. The hsa-miR-4667-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, the precursor of "hsa-miR-4667-5p" is known to be "hsa-mir-4667" (miRBase Accession No. MI0017297, SEQ ID NO: 373), which has a hairpin-like structure.
[0247] As used herein, the term "hsa-miR-135a-3p gene" or "hsa-miR-135a-3p" encompasses the hsa-miR-135a-3p gene set forth in SEQ ID NO: 176 (miRBase Accession No. MIMAT0004595) as well as homologs or orthologs from other organisms. The hsa-miR-135a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, vol. 12, pp. 735-739. Furthermore, "hsa-miR-135a-3p" is known to have a precursor, "hsa-mir-135a-1" (miRBase Accession No. MI0000452, SEQ ID NO: 374), which has a hairpin-like structure.
[0248] As used herein, the term "hsa-miR-4486 gene" or "hsa-miR-4486" encompasses the hsa-miR-4486 gene set forth in SEQ ID NO: 177 (miRBase Accession No. MIMAT0019020) as well as homologs or orthologs from other species. The hsa-miR-4486 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4486" is "hsa-mir-4486" (miRBase Accession No. MI0016847, SEQ ID NO: 375), which has a hairpin-like structure.
[0249] As used herein, the term "hsa-miR-4697-5p gene" or "hsa-miR-4697-5p" encompasses the hsa-miR-4697-5p gene set forth in SEQ ID NO: 178 (miRBase Accession No. MIMAT0019791) and homologs or orthologs from other organisms. The hsa-miR-4697-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. It is also known that the precursor of "hsa-miR-4697-5p" is "hsa-mir-4697" (miRBase Accession No. MI0017330, SEQ ID NO: 376), which has a hairpin-like structure.
[0250] As used herein, the term "hsa-miR-4725-3p gene" or "hsa-miR-4725-3p" encompasses the hsa-miR-4725-3p gene set forth in SEQ ID NO: 179 (miRBase Accession No. MIMAT0019844) as well as homologs or orthologs from other organisms. The hsa-miR-4725-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, the precursor of "hsa-miR-4725-3p" is known to be "hsa-mir-4725" (miRBase Accession No. MI0017362, SEQ ID NO: 377), which has a hairpin-like structure.
[0251] As used herein, the term "hsa-miR-6510-5p gene" or "hsa-miR-6510-5p" encompasses the hsa-miR-6510-5p gene set forth in SEQ ID NO: 180 (miRBase Accession No. MIMAT0025476) as well as homologs or orthologs from other organisms. The hsa-miR-6510-5p gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet, vol. 20, pp. 4025-4040. Furthermore, the precursor of "hsa-miR-6510-5p" is known to be "hsa-mir-6510" (miRBase Accession No. MI0022222, SEQ ID NO: 378), which has a hairpin-like structure.
[0252] As used herein, the terms "hsa-miR-5001-5p gene" or "hsa-miR-5001-5p" encompass the hsa-miR-5001-5p gene set forth in SEQ ID NO: 181 (miRBase Accession No. MIMAT0021021) and homologs or orthologs from other organisms. The hsa-miR-5001-5p gene can be obtained by the method described in Hansen TB et al., 2011, RNA Biol, Vol. 8, pp. 378-383. Furthermore, "hsa-miR-5001-5p" is known to have a precursor, "hsa-mir-5001" (miRBase Accession No. MI0017867, SEQ ID NO: 379), which has a hairpin-like structure.
[0253] As used herein, the term "hsa-miR-4673 gene" or "hsa-miR-4673" encompasses the hsa-miR-4673 gene set forth in SEQ ID NO: 182 (miRBase Accession No. MIMAT0019755) as well as homologs or orthologs from other organisms. The hsa-miR-4673 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4673" is "hsa-mir-4673" (miRBase Accession No. MI0017304, SEQ ID NO: 380), which has a hairpin-like structure.
[0254] As used herein, the term "hsa-miR-4466 gene" or "hsa-miR-4466" encompasses the hsa-miR-4466 gene set forth in SEQ ID NO: 183 (miRBase Accession No. MIMAT0018993) as well as homologs or orthologs from other biological species. The hsa-miR-4466 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4466" is "hsa-mir-4466" (miRBase Accession No. MI0016817, SEQ ID NO: 381), which has a hairpin-like structure.
[0255] As used herein, the term "hsa-miR-23a-3p gene" or "hsa-miR-23a-3p" encompasses the hsa-miR-23a-3p gene set forth in SEQ ID NO: 184 (miRBase Accession No. MIMAT0000078) as well as homologs or orthologs from other organisms. The hsa-miR-23a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science, Vol. 294, pp. 853-858. It is also known that the precursor of "hsa-miR-23a-3p" is "hsa-mir-23a" (miRBase Accession No. MI0000079, SEQ ID NO: 382), which has a hairpin-like structure.
[0256] As used herein, the term "hsa-miR-3656 gene" or "hsa-miR-3656" encompasses the hsa-miR-3656 gene set forth in SEQ ID NO: 185 (miRBase Accession No. MIMAT0018076) as well as homologs or orthologs from other organisms. The hsa-miR-3656 gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, pp. 6234-6246. Furthermore, a known precursor of "hsa-miR-3656" is "hsa-mir-3656" (miRBase Accession No. MI0016056, SEQ ID NO: 383), which has a hairpin-like structure.
[0257] As used herein, the term "hsa-miR-6782-5p gene" or "hsa-miR-6782-5p" encompasses the hsa-miR-6782-5p gene set forth in SEQ ID NO: 186 (miRBase Accession No. MIMAT0027464) as well as homologs or orthologs from other organisms. The hsa-miR-6782-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6782-5p" is known to be "hsa-mir-6782" (miRBase Accession No. MI0022627, SEQ ID NO: 384), which has a hairpin-like structure.
[0258] As used herein, the term "hsa-miR-4689 gene" or "hsa-miR-4689" encompasses the hsa-miR-4689 gene set forth in SEQ ID NO: 187 (miRBase Accession No. MIMAT0019778) as well as homologs or orthologs from other organisms. The hsa-miR-4689 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, a known precursor of "hsa-miR-4689" is "hsa-mir-4689" (miRBase Accession No. MI0017322, SEQ ID NO: 385), which has a hairpin-like structure.
[0259] As used herein, the term "hsa-miR-451a gene" or "hsa-miR-451a" encompasses the hsa-miR-451a gene set forth in SEQ ID NO: 188 (miRBase Accession No. MIMAT0001631) and homologs or orthologs from other organisms. The hsa-miR-451a gene can be obtained by the method described in Altuvia Y et al., 2005, Nucleic Acids Res, 33, pp. 2697-2706. Furthermore, "hsa-miR-451a" is known to have a precursor, "hsa-mir-451a" (miRBase Accession No. MI0001729, SEQ ID NO: 386), which has a hairpin-like structure.
[0260] As used herein, the term "hsa-miR-4446-3p gene" or "hsa-miR-4446-3p" encompasses the hsa-miR-4446-3p gene set forth in SEQ ID NO: 189 (miRBase Accession No. MIMAT0018965) as well as homologs or orthologs from other organisms. The hsa-miR-4446-3p gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. It is also known that the precursor of "hsa-miR-4446-3p" is "hsa-mir-4446" (miRBase Accession No. MI0016789, SEQ ID NO: 387), which has a hairpin-like structure.
[0261] As used herein, the term "hsa-miR-3180-3p gene" or "hsa-miR-3180-3p" encompasses the hsa-miR-3180-3p gene set forth in SEQ ID NO: 190 (miRBase Accession No. MIMAT0015058) and homologs or orthologs from other organisms. The hsa-miR-3180-3p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Furthermore, "hsa-miR-3180-3p" is known to have precursors that have hairpin-like structures, "hsa-mir-3180-1, hsa-mir-3180-2, hsa-mir-3180-3" (miRBase Accession Nos. MI0014214, MI0014215, MI0014217, SEQ ID NOs: 388, 389, 390).
[0262] As used herein, the term "hsa-miR-642a-3p gene" or "hsa-miR-642a-3p" encompasses the hsa-miR-642a-3p gene set forth in SEQ ID NO: 191 (miRBase Accession No. MIMAT0020924) and homologs or orthologs from other organisms. The hsa-miR-642a-3p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103, pp. 3687-3692. Furthermore, the precursor of "hsa-miR-642a-3p" is known to be "hsa-mir-642a" (miRBase Accession No. MI0003657, SEQ ID NO: 391), which has a hairpin-like structure.
[0263] As used herein, the term "hsa-miR-6889-5p gene" or "hsa-miR-6889-5p" encompasses the hsa-miR-6889-5p gene set forth in SEQ ID NO: 192 (miRBase Accession No. MIMAT0027678) and homologs or orthologs from other organisms. The hsa-miR-6889-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6889-5p" is known to be "hsa-mir-6889" (miRBase Accession No. MI0022736, SEQ ID NO: 392), which has a hairpin-like structure.
[0264] As used herein, the term "hsa-miR-3178 gene" or "hsa-miR-3178" encompasses the hsa-miR-3178 gene set forth in SEQ ID NO: 193 (miRBase Accession No. MIMAT0015055) as well as homologs or orthologs from other organisms. The hsa-miR-3178 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. Furthermore, "hsa-miR-3178" is known to have a precursor, "hsa-mir-3178" (miRBase Accession No. MI0014212, SEQ ID NO: 393), which has a hairpin-like structure.
[0265] As used herein, the term "hsa-miR-4665-5p gene" or "hsa-miR-4665-5p" encompasses the hsa-miR-4665-5p gene set forth in SEQ ID NO: 194 (miRBase Accession No. MIMAT0019739) as well as homologs or orthologs from other organisms. The hsa-miR-4665-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, the precursor of "hsa-miR-4665-5p" is known to be "hsa-mir-4665" (miRBase Accession No. MI0017295, SEQ ID NO: 323), which has a hairpin-like structure.
[0266] As used herein, the term "hsa-miR-6722-3p gene" or "hsa-miR-6722-3p" encompasses the hsa-miR-6722-3p gene set forth in SEQ ID NO: 195 (miRBase Accession No. MIMAT0025854) as well as homologs or orthologs from other organisms. The hsa-miR-6722-3p gene can be obtained by the method described in Li Y et al., 2012, Gene, vol. 497, pp. 330-335. It is also known that the precursor of "hsa-miR-6722-3p" is "hsa-mir-6722" (miRBase Accession No. MI0022557, SEQ ID NO: 394), which has a hairpin-like structure.
[0267] As used herein, the term "hsa-miR-30c-1-3p gene" or "hsa-miR-30c-1-3p" encompasses the hsa-miR-30c-1-3p gene set forth in SEQ ID NO: 196 (miRBase Accession No. MIMAT0004674) as well as homologs or orthologs from other organisms. The hsa-miR-30c-1-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, vol. 12, pp. 735-739. Furthermore, the precursor of "hsa-miR-30c-1-3p" is known to be "hsa-mir-30c-1" (miRBase Accession No. MI0000736, SEQ ID NO: 395), which has a hairpin-like structure.
[0268] As used herein, the term "hsa-miR-4507 gene" or "hsa-miR-4507" encompasses the hsa-miR-4507 gene set forth in SEQ ID NO: 197 (miRBase Accession No. MIMAT0019044) as well as homologs or orthologs from other biological species. The hsa-miR-4507 gene can be obtained by the method described in Jima DD et al., 2010, Blood, vol. 116, e118-e127. Furthermore, "hsa-miR-4507" is known to have a precursor, "hsa-mir-4507" (miRBase Accession No. MI0016871, SEQ ID NO: 396), which has a hairpin-like structure.
[0269] As used herein, the term "hsa-miR-3141 gene" or "hsa-miR-3141" encompasses the hsa-miR-3141 gene set forth in SEQ ID NO: 198 (miRBase Accession No. MIMAT0015010) and homologs or orthologs from other organisms. The hsa-miR-3141 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. It is also known that "hsa-miR-3141" has a precursor, "hsa-mir-3141" (miRBase Accession No. MI0014165, SEQ ID NO: 397), which has a hairpin-like structure.
[0270] As used herein, the term "hsa-miR-1199-5p gene" or "hsa-miR-1199-5p" encompasses the hsa-miR-1199-5p gene set forth in SEQ ID NO: 199 (miRBase Accession No. MIMAT0031119) as well as homologs or orthologs from other organisms. The hsa-miR-1199-5p gene can be obtained by the method described in Salvi A et al., 2013, Int J Oncol, vol. 42, pp. 391-402. Furthermore, the precursor of "hsa-miR-1199-5p" is known to be "hsa-mir-1199" (miRBase Accession No. MI0020340, SEQ ID NO: 398), which has a hairpin-like structure.
[0271] As used herein, the term "hsa-miR-6794-5p gene" or "hsa-miR-6794-5p" encompasses the hsa-miR-6794-5p gene set forth in SEQ ID NO: 635 (miRBase Accession No. MIMAT0027488) and homologs or orthologs from other biological species. The hsa-miR-6794-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6794-5p" is known to be "hsa-mir-6794" (miRBase Accession No. MI0022639, SEQ ID NO: 643), which has a hairpin-like structure.
[0272] As used herein, the term "hsa-miR-6774-5p gene" or "hsa-miR-6774-5p" encompasses the hsa-miR-6774-5p gene set forth in SEQ ID NO: 636 (miRBase Accession No. MIMAT0027448) and homologs or orthologs from other biological species. The hsa-miR-6774-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6774-5p" is known to be "hsa-mir-6774" (miRBase Accession No. MI0022619, SEQ ID NO: 644), which has a hairpin-like structure.
[0273] As used herein, the terms "hsa-miR-4707-3p gene" or "hsa-miR-4707-3p" encompass the hsa-miR-4707-3p gene set forth in SEQ ID NO: 637 (miRBase Accession No. MIMAT0019808) and homologs or orthologs from other biological species. The hsa-miR-4707-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, the precursor of "hsa-miR-4707-3p" is known to be "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 645), which has a hairpin-like structure.
[0274] As used herein, the term "hsa-miR-4534 gene" or "hsa-miR-4534" encompasses the hsa-miR-4534 gene set forth in SEQ ID NO: 638 (miRBase Accession No. MIMAT0019073) and homologs or orthologs from other biological species. The hsa-miR-4534 gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4534" is "hsa-mir-4534" (miRBase Accession No. MI0016901, SEQ ID NO: 646), which has a hairpin-like structure.
[0275] As used herein, the term "hsa-miR-4294 gene" or "hsa-miR-4294" encompasses the hsa-miR-4294 gene set forth in SEQ ID NO: 639 (miRBase Accession No. MIMAT0016849) as well as homologs or orthologs from other biological species. The hsa-miR-4294 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One., vol. 4, e7192. Furthermore, a known precursor of "hsa-miR-4294" is "hsa-mir-4294" (miRBase Accession No. MI0015827, SEQ ID NO: 647), which has a hairpin-like structure.
[0276] As used herein, the terms "hsa-miR-6850-5p gene" or "hsa-miR-6850-5p" encompass the hsa-miR-6850-5p gene set forth in SEQ ID NO: 640 (miRBase Accession No. MIMAT0027600) and homologs or orthologs from other biological species. The hsa-miR-6850-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6850-5p" is known to be "hsa-mir-6850" (miRBase Accession No. MI0022696, SEQ ID NO: 648), which has a hairpin-like structure.
[0277] As used herein, the term "hsa-miR-6089 gene" or "hsa-miR-6089" encompasses the hsa-miR-6089 gene set forth in SEQ ID NO: 641 (miRBase Accession No. MIMAT0023714) and homologs or orthologs from other biological species. The hsa-miR-6089 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, vol. 21, pp. 2049-2057. Furthermore, "hsa-miR-6089" is known to have precursors with hairpin-like structures, "hsa-mir-6089-1" and "hsa-mir-6089-2" (miRBase Accession Nos. MI0020366 and MI0023563, SEQ ID NOs: 649 and 650).
[0278] As used herein, the terms "hsa-miR-671-5p gene" or "hsa-miR-671-5p" encompass the hsa-miR-671-5p gene set forth in SEQ ID NO: 642 (miRBase Accession No. MIMAT0003880) and homologs or orthologs from other organisms. The hsa-miR-671-5p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, vol. 16, pp. 1289-1298. Furthermore, the precursor of "hsa-miR-671-5p" is known to be "hsa-mir-671" (miRBase Accession No. MI0003760, SEQ ID NO: 651), which has a hairpin-like structure.
[0279] Furthermore, when mature miRNAs are excised from RNA precursors with hairpin-like structures, one to several bases before or after the sequence may be shortened or lengthened, or base substitutions may occur, resulting in mutants called isomiRs (Morin RD. et al., 2008, Genome Res., Vol. 18, pp. 610-621). In addition to the nucleotide sequences represented by SEQ ID NOS: 1-199 and 635-642, miRBase Release 20 also lists numerous mutants and fragments of the nucleotide sequences represented by SEQ ID NOS: 399-634 and 652-657, known as isomiRs. These mutants can also be obtained as miRNAs having the nucleotide sequences represented by SEQ ID NOS: 1-199 and 635-642.
[0280] That is, SEQ ID NOs: 3, 4, 11, 13, 14, 18, 20, 21, 26, 29, 35, 36, 39, 41, 42, 45, 46, 47, 48, 49, 51, 53, 54, 55, 56, 57, 58, 59, 60, 62, 65, 66, 67, 68, 71, 72, 73, 74, 75, 76, 78, 82, 83, 88, 90, 91, 92, 94, 95, 98, 99, 101, 102, 103, 104, 106, 107, 108, 109, 110, 113, 116, 117, 118, 120, 121, 122, 123, 125, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 190, 191, 193, 194, 196, 197, 198, 637, 641 and 642, or variants of polynucleotides consisting of the nucleotide sequences represented by the following nucleotide sequences in which u is replaced by t, for example, miRBase ReleaseThe longest variants registered in 20 are SEQ ID NOs: 399, 401, 403, 405, 407, 409, 411, 413, 415, 417, 419, 421, 423, 425, 427, 429, 431, 433, 435, 437, 439, 441, 443, 445, 447, 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 471, 473, 475, 477, 479, 481, 483, 485, 487, 489, 491, 493, 495, 497, 499, 501, 503, 505, 507, 509, 511, 513, 515, 516 17, 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, 58 3, 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, 652, 654 and 656.
[0281] Also, SEQ ID NOS: 3, 4, 11, 13, 14, 18, 20, 21, 26, 29, 35, 36, 39, 41, 42, 45, 46, 47, 48, 49, 51, 53, 54, 55, 56, 57, 58, 59, 60, 62, 65, 66, 67, 68, 71, 72, 73, 74, 75, 76, 78, 82, 83, 88, 90, 91, 92, 94, 95, 98, 99, 101, 102, 103, 104, 106, 107, 108, 109, 110, 113, 116, 117, 118, 120, 121, 122, 123, 125, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 190, 191, 193, 194, 196, 197, 198, 637, 641, and 642, or a polynucleotide consisting of the base sequence represented by the following base sequences in which u is replaced by t, for example, miRBase ReleaseThe shortest variants registered in 20 are SEQ ID NOs: 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532 52, 454, 456, 458, 460, 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518 , 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, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654 Examples of polynucleotides containing the nucleotide sequences represented by SEQ ID NOs: 1 to 199 and 635 to 642 include polynucleotides having the sequences represented by SEQ ID NOs: 86, 588, 590, 592, 594, 596, 598, 600, 602, 604, 606, 608, 610, 612, 614, 616, 618, 620, 622, 624, 626, 628, 630, 632, 634, 653, 655, and 657. In addition to these variants and fragments, examples of polynucleotides containing the nucleotide sequences represented by SEQ ID NOs: 1 to 199 and 635 to 642 include the polynucleotides represented by SEQ ID NOs: 200 to 398 and 643 to 651, which are precursors of the nucleotide sequences.
[0282] Table 1 shows the names of the genes represented by SEQ ID NOs: 1 to 657 and their miRBase Accession Nos. (registration numbers).
[0283] As used herein, the term "capable of specifically binding" means that the nucleic acid probe or primer used in the present invention binds to a specific target nucleic acid and is substantially incapable of binding to other nucleic acids.
[0284] [Table 1]
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[0302] This specification includes part or all of the contents as disclosed in the specifications and / or drawings of Japanese Patent Application Nos. 2014-123224 and 2015-071485, which are priority documents of this application. [Effects of the Invention]
[0303] The present invention makes it possible to detect stomach cancer easily and with high accuracy.
[0304] For example, whether a patient has stomach cancer can be easily detected by using the measured values of several miRNAs in the patient's blood, serum, and / or plasma, which can be collected minimally invasively, as an indicator. [Brief explanation of the drawings]
[0305] [Figure 1] This figure shows the relationship between the base sequences of hsa-miR-1225-3p (represented by sequence number 7) and hsa-miR-1225-5p (represented by sequence number 52), which are generated from the precursor hsa-mir-1225 (represented by sequence number 206). [Figure 2]Left: The vertical axis shows the measured values of hsa-miR-4257 (SEQ ID NO: 1) for healthy subjects (100 individuals) and gastric cancer patients (34 individuals) selected as the training sample group. The horizontal line in the figure indicates the threshold (6.29) for discriminating between the two groups, optimized by Fisher's discriminant analysis. Right: The vertical axis shows the measured values of hsa-miR-4257 (SEQ ID NO: 1) for healthy subjects (50 individuals) and gastric cancer patients (16 individuals) selected as the test sample group. The horizontal line in the figure indicates the threshold (6.29) for discriminating between the two groups, set in the training sample group. [Figure 3] Left: The horizontal axis shows the measured values of hsa-miR-4257 (SEQ ID NO: 1) and the vertical axis shows the measured values of hsa-miR-6726-5p (SEQ ID NO: 2) for healthy individuals (100 individuals, circles) and gastric cancer patients (34 individuals, triangles) selected as the training sample group. The line in the figure represents the discriminant function (0 = 0.83x + y - 14.78) that discriminated between the two groups, optimized by Fisher's discriminant analysis. Right: The horizontal axis shows the measured values of hsa-miR-4257 (SEQ ID NO: 1) and the vertical axis shows the measured values of hsa-miR-6726-5p (SEQ ID NO: 2) for healthy individuals (50 individuals, circles) and gastric cancer patients (16 individuals, triangles) selected as the test sample group. The line in the figure represents the threshold (0 = 0.83x + y - 14.78) that discriminated between the two groups, set in the training sample group. [Figure 4]Upper figure: hsa-miR-6781-5p (SEQ ID NO: 9), hsa-miR-204-3p (SEQ ID NO: 13), hsa-miR-3195 (SEQ ID NO: 143), hsa-miR-6769b-5p (SEQ ID NO: 155), hsa-miR-4665-5p (SEQ ID NO: 194 ... Using Fisher's discriminant analysis from the measured values of miR-4294 (SEQ ID NO: 639), a discriminant equation (2.51 × hsa-miR-6781-5p-0.63 × hsa-miR-4419b + 0.98 × hsa-miR-940 + 0.63 × hsa-miR-4294-0.70 × hsa-miR-6769b-5p + 0.85 × hsa-miR-1914-3p-37.81) was created, and the discriminant score obtained from the discriminant equation is plotted on the vertical axis and the sample group on the horizontal axis. The dotted line in the figure indicates the discriminant boundary for discriminating between both groups where the discriminant score is 0. The figure below shows the discriminant scores obtained from the discriminant equation for the training sample group for the measured values of hsa-miR-6781-5p (SEQ ID NO: 9), hsa-miR-204-3p (SEQ ID NO: 13), hsa-miR-3195 (SEQ ID NO: 143), hsa-miR-6769b-5p (SEQ ID NO: 155), hsa-miR-4665-5p (SEQ ID NO: 194), and hsa-miR-4294 (SEQ ID NO: 639) in the test sample group consisting of 16 gastric cancer patients, 48 healthy subjects, 37 pancreatic cancer patients, 33 biliary tract cancer patients, 15 colorectal cancer patients, 20 liver cancer patients, and 4 patients with benign pancreatic and biliary diseases. The vertical axis represents the discriminant score obtained from the discriminant equation for the training sample group, and the horizontal axis represents the sample group. The dotted line in the figure indicates the discriminant boundary for discriminating between the two groups, where the discriminant score is 0. DETAILED DESCRIPTION OF THE INVENTION
[0306] The present invention will be described in more detail below. 1. Target nucleic acid for gastric cancer Major target nucleic acids as gastric cancer markers for detecting the presence and / or absence of gastric cancer or gastric cancer cells using the nucleic acid probes or primers for detecting gastric cancer defined above of the present invention include hsa-miR-4257, hsa-miR-6726-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-6787-5p, hsa-miR-6875-5p, hsa-miR-1225-3p, hsa-miR-8063, hsa-miR-6781-5p, hsa-miR-4746-3p, hsa-miR-1225 ... -1908-5p, hsa-miR-6756-5p, hsa-miR-204-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-6825-5p, hsa-miR-7108-5p, hsa-miR-4792, hsa-miR-76 41, hsa-miR-3188, hsa-miR-3131, hsa-miR-6780b-5p, hsa-miR-8069, hsa-miR-6840-3p, hsa-miR-8072, hsa-miR-1233-5p, hsa-miR-6887-5p, hsa- miR-1231, hsa-miR-5572, hsa-miR-6738-5p, hsa-miR-6784-5p, hsa-miR-6791-5p, hsa-miR-6749-5p, hsa-miR-6741-5p, hsa-miR-128-1-5p, hsa- miR-4419b, hsa-miR-6746-5p, hsa-miR-3184-5p, hsa-miR-3679-5p, hsa-miR-7110-5p, hsa-miR-4516, hsa-miR-6717-5p, hsa-miR-6826-5p, hsa-m iR-4433b-3p, hsa-miR-3679-3p, hsa-miR-3135b, hsa-miR-3622a-5p, hsa-miR-711, hsa-miR-4467, hsa-miR-6857-5p, hsa-miR-6515-3p, hsa-miR- 1225-5p, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-642b-3p, hsa-miR-1249, hsa-miR-744-5p, hsa-miR-4442, hsa-miR-1228-3p, hsa-miR-939-5p,hsa-miR-6845-5p, hsa-miR-887-3p, hsa-miR-7845-5p, hsa-miR-6729-5p, hsa-miR-4632-5p, hsa-miR-615-5p, hsa-miR-6724-5p, hsa-miR-4728-5p, hsa-miR-6732-5p, hsa-miR-6816-5p, hsa-miR-4695-5p, hsa-miR-6088, hsa-miR-7975, hsa-miR-3197, hsa-miR-6125, hsa-miR-4433-3p, hsa- miR-6727-5p, hsa-miR-4706, hsa-miR-7847-3p, hsa-miR-6805-3p, hsa-miR-6766-3p, hsa-miR-1913, hsa-miR-4649-5p, hsa-miR-602, hsa-miR-3 663-3p, hsa-miR-6893-5p, hsa-miR-6861-5p, hsa-miR-4449, hsa-miR-6842-5p, hsa-miR-4454, hsa-miR-5195-3p, hsa-miR-663b, hsa-miR-6765-5 p, hsa-miR-4513, hsa-miR-614, hsa-miR-6785-5p, hsa-miR-6777-5p, hsa-miR-940, hsa-miR-4741, hsa-miR-6870-5p, hsa-miR-6131, hsa-miR-15 0-3p, hsa-miR-4707-5p, hsa-miR-1915-3p, hsa-miR-3937, hsa-miR-937-5p, hsa-miR-4443, hsa-miR-1914-3p, hsa-miR-3620-5p, hsa-miR-1268b hsa-miR-1227-5p, hsa-miR-6880-5p, hsa-miR-4417, hsa-miR-6802-5p, hsa-miR-6769a-5p, hsa-miR-663a, hsa-miR-6721-5p, hsa-miR-4532, hsa -miR-7977、hsa-miR-92b-5p、hsa-miR-371a-5p、hsa-miR-6126、hsa-miR-4734、hsa-miR-4665-3p、hsa-miR-423-5p、hsa-miR-1469、hsa-miR-4675、hsa-miR-1915-5p, hsa-miR-6716-5p, hsa-miR-718, hsa-miR-4281, hsa-miR-6820-5p, hsa-miR-6795- 5p, hsa-miR-6779-5p, hsa-miR-7109-5p, hsa-miR-6798-5p, hsa-miR-4648, hsa-miR-8059, hsa-miR-67 65-3p, hsa-miR-6132, hsa-miR-4492, hsa-miR-7107-5p, hsa-miR-3195, hsa-miR-3180, hsa-miR-296- 3p, hsa-miR-564, hsa-miR-1268a, hsa-miR-6848-5p, hsa-miR-762, hsa-miR-2861, hsa-miR-1203, hsa- miR-1260b, hsa-miR-4476, hsa-miR-6885-5p, hsa-miR-6769b-5p, hsa-miR-23b-3p, hsa-miR-1343-5p , hsa-miR-3621, hsa-miR-4688, hsa-miR-4286, hsa-miR-4640-5p, hsa-miR-4739, hsa-miR-1260a, hsa- At least one or more miRNAs selected from the group consisting of miR-4276, hsa-miR-7106, hsa-miR-6794-5p, hsa-miR-6774-5p, hsa-miR-4707-3p, hsa-miR-4534, hsa-miR-4294, hsa-miR-6850-5p, hsa-miR-6089, and hsa-miR-671-5p are included. Furthermore, other gastric cancer markers that can be combined with these miRNAs, i.e., at least one or more miRNAs selected from the group consisting of hsa-miR-128-2-5p, hsa-miR-125a-3p, hsa-miR-92a-2-5p, and hsa-miR-486-3p, can also be preferably used as target nucleic acids. Furthermore, other gastric cancer markers that can be combined with these miRNAs, namely, hsa-miR-3196, hsa-miR-211-3p, hsa-miR-4271, hsa-miR-6851-5p, hsa-miR-149-3p, hsa-miR-4667-5p, hsa-miR-135a-3p,hsa-miR-4486, hsa-miR-4697-5p, hsa-miR-4725-3p, hsa-miR-6510-5p, hsa-miR-5001-5p, hsa-miR-4673, hsa-miR -4466, hsa-miR-23a-3p, hsa-miR-3656, hsa-miR-6782-5p, hsa-miR-4689, hsa-miR-451a, hsa-miR-4446-3p, hsa-mi At least one miRNA selected from the group consisting of hsa-miR-3180-3p, hsa-miR-642a-3p, hsa-miR-6889-5p, hsa-miR-3178, hsa-miR-4665-5p, hsa-miR-6722-3p, hsa-miR-30c-1-3p, hsa-miR-4507, hsa-miR-3141, and hsa-miR-1199-5p can also be preferably used as the target nucleic acid.
[0307] The above miRNAs include, for example, human genes containing the nucleotide sequences represented by any of SEQ ID NOs: 1 to 199 and 635 to 642 (i.e., hsa-miR-4257, hsa-miR-6726-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-6787-5p, hsa-miR-6875-5p, hsa-miR-1225-3p, hsa-miR-8063, hsa-miR-6781-5p, hsa-miR-4746-3p, hsa-miR-1908-5p, and hsa-miR-6756-5p, respectively). p, hsa-miR-204-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-6825-5p, hsa-miR-7108-5p, hsa-miR-4792, hsa-miR-7641, hsa-miR-3188, hsa-miR- 3131, hsa-miR-6780b-5p, hsa-miR-8069, hsa-miR-6840-3p, hsa-miR-8072, hsa-miR-1233-5p, hsa-miR-6887-5p, hsa-miR-1231, hsa-miR-5572, hsa -miR-6738-5p, hsa-miR-6784-5p, hsa-miR-6791-5p, hsa-miR-6749-5p, hsa-miR-6741-5p, hsa-miR-128-1-5p, hsa-miR-4419b, hsa-miR-6746-5p, h sa-miR-3184-5p, hsa-miR-3679-5p, hsa-miR-7110-5p, hsa-miR-4516, hsa-miR-6717-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-3679-3p, hsa-miR-3135b, hsa-miR-3622a-5p, hsa-miR-711, hsa-miR-4467, hsa-miR-6857-5p, hsa-miR-6515-3p, hsa-miR-1225-5p, hsa-miR-187-5p, hsa-mi R-3185, hsa-miR-642b-3p, hsa-miR-1249, hsa-miR-744-5p, hsa-miR-4442, hsa-miR-1228-3p, hsa-miR-939-5p, hsa-miR-6845-5p, hsa-miR-887-3p,hsa-miR-7845-5p, hsa-miR-6729-5p, hsa-miR-4632-5p, hsa-miR-615-5p, hsa-miR-6724-5p, hsa-miR-4728-5p, hsa-miR-6732-5p, hsa-miR-6816-5 p, hsa-miR-4695-5p, hsa-miR-6088, hsa-miR-7975, hsa-miR-3197, hsa-miR-6125, hsa-miR-4433-3p, hsa-miR-6727-5p, hsa-miR-4706, hsa-miR-78 47-3p, hsa-miR-6805-3p, hsa-miR-6766-3p, hsa-miR-1913, hsa-miR-4649-5p, hsa-miR-602, hsa-miR-3663-3p, hsa-miR-6893-5p, hsa-miR-6861-5 p, hsa-miR-4449, hsa-miR-6842-5p, hsa-miR-4454, hsa-miR-5195-3p, hsa-miR-663b, hsa-miR-6765-5p, hsa-miR-4513, hsa-miR-614, hsa-miR-678 5-5p, hsa-miR-6777-5p, hsa-miR-940, hsa-miR-4741, hsa-miR-6870-5p, hsa-miR-6131, hsa-miR-150-3p, hsa-miR-4707-5p, hsa-miR-1915-3p, hsa -miR-3937、hsa-miR-937-5p、hsa-miR-4443、hsa-miR-1914-3p、hsa-miR-3620-5p、hsa-miR-1268b、hsa-miR-1227-5p、hsa-miR-6880-5p、hsa-miR-4 417、hsa-miR-6802-5p、hsa-miR-6769a-5p、hsa-miR-663a、hsa-miR-6721 -5p、hsa-miR-4532、hsa-miR-7977、hsa-miR-92b-5p、hsa-miR-371a-5p、hs a-miR-6126, hsa-miR-4734, hsa-miR-4665-3p, hsa-miR-423-5p, hsa-miR-1469, hsa-miR-4675, hsa-miR-1915-5p, hsa-miR-6716-5p, hsa-miR-718hsa-miR-4281, hsa-miR-6820-5p, hsa-miR-6795-5p, hsa-miR-6779-5p, hsa-miR-7109-5p, hsa-miR-6798-5p, hsa-miR-4648, hsa-miR-8059, hsa-miR-6765-3p, hsa-miR-6132, hsa-miR-4492, hsa-miR-7107-5p, hsa-miR-3195, hsa-miR-3180, hsa-miR-296-3p, hsa-miR-564, hsa-miR-1268a, hsa -miR-6848-5p, hsa-miR-762, hsa-miR-2861, hsa-miR-1203, hsa-miR-1260b, hsa-miR-4476, hsa-miR-6885-5p, hsa-miR-6769b-5p, hsa-miR-23b- 3p, hsa-miR-1343-5p, hsa-miR-3621, hsa-miR-4688, hsa-miR-4286, hsa-miR-4640-5p, hsa-miR-4739, hsa-miR-1260a, hsa-miR-4276, hsa-miR-71 06, hsa-miR-6794-5p, hsa-miR-6774-5p, hsa-miR-4707-3p, hsa-miR-4534, hsa-miR-4294, hsa-miR-6850-5p, hsa-miR-6089, hsa-miR-671-5p, hs a-miR-128-2-5p, hsa-miR-125a-3p, hsa-miR-92a-2-5p, hsa-miR-486-3p, hsa-miR-3196, hsa-miR-211-3p, hsa-miR-4271, hsa-miR-6851-5p, hsa- miR-149-3p, hsa-miR-4667-5p, hsa-miR-135a-3p, hsa-miR-4486, hsa-miR-4697-5p, hsa-miR-4725-3p, hsa-miR-6510-5p, hsa-miR-5001-5p, hsa- miR-4673, hsa-miR-4466, hsa-miR-23a-3p, hsa-miR-3656, hsa-miR-6782-5p, hsa-miR-4689, hsa-miR-451a, hsa-miR-4446-3p, hsa-miR-3180-3pThese include miR-642a-3p, hsa-miR-6889-5p, hsa-miR-3178, hsa-miR-4665-5p, hsa-miR-6722-3p, hsa-miR-30c-1-3p, hsa-miR-4507, hsa-miR-3141, and hsa-miR-1199-5p), their homologs, their transcription products, and their variants or derivatives, where gene, homolog, transcription product, variant, and derivative are as defined above.
[0308] Preferred target nucleic acids are human genes comprising the nucleotide sequence shown in any of SEQ ID NOs: 1 to 657, or transcription products thereof, more preferably such transcription products, ie, miRNAs, or their precursor RNAs, pri-miRNAs or pre-miRNAs.
[0309] The first target gene is the hsa-miR-4257 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0310] The second target gene is the hsa-miR-6726-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0311] The third target gene is the hsa-miR-1343-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0312] The fourth target gene is the hsa-miR-1247-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0313] The fifth target gene is the hsa-miR-6787-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0314] The sixth target gene is the hsa-miR-6875-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0315] The seventh target gene is the hsa-miR-1225-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0316] The eighth target gene is the hsa-miR-8063 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0317] The ninth target gene is the hsa-miR-6781-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0318] The tenth target gene is the hsa-miR-4746-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0319] The eleventh target gene is the hsa-miR-1908-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0320] The twelfth target gene is the hsa-miR-6756-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0321] The thirteenth target gene is the hsa-miR-204-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0322] The 14th target gene is the hsa-miR-4651 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0323] The 15th target gene is the hsa-miR-6757-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0324] The 16th target gene is the hsa-miR-6825-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0325] The 17th target gene is the hsa-miR-7108-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0326] The 18th target gene is the hsa-miR-4792 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0327] The 19th target gene is the hsa-miR-7641 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0328] The 20th target gene is the hsa-miR-3188 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0329] The 21st target gene is the hsa-miR-3131 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0330] The 22nd target gene is the hsa-miR-6780b-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0331] The 23rd target gene is the hsa-miR-8069 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0332] The 24th target gene is the hsa-miR-6840-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0333] The 25th target gene is the hsa-miR-8072 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0334] The 26th target gene is the hsa-miR-1233-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0335] The 27th target gene is the hsa-miR-6887-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0336] The 28th target gene is the hsa-miR-1231 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0337] The 29th target gene is the hsa-miR-5572 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0338] The 30th target gene is the hsa-miR-6738-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0339] The 31st target gene is the hsa-miR-6784-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0340] The 32nd target gene is the hsa-miR-6791-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0341] The 33rd target gene is the hsa-miR-6749-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0342] The 34th target gene is the hsa-miR-6741-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0343] The 35th target gene is the hsa-miR-128-1-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0344] The 36th target gene is the hsa-miR-4419b gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0345] The 37th target gene is the hsa-miR-6746-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0346] The 38th target gene is the hsa-miR-3184-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0347] The 39th target gene is the hsa-miR-3679-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0348] The 40th target gene is the hsa-miR-7110-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0349] The 41st target gene is the hsa-miR-4516 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0350] The 42nd target gene is the hsa-miR-6717-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0351] The 43rd target gene is the hsa-miR-6826-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0352] The 44th target gene is the hsa-miR-4433b-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0353] The 45th target gene is the hsa-miR-3679-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0354] The 46th target gene is the hsa-miR-3135b gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0355] The 47th target gene is the hsa-miR-3622a-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0356] The 48th target gene is the hsa-miR-711 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0357] The 49th target gene is the hsa-miR-4467 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0358] The 50th target gene is the hsa-miR-6857-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0359] The 51st target gene is the hsa-miR-6515-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0360] The 52nd target gene is the hsa-miR-1225-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0361] The 53rd target gene is the hsa-miR-187-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0362] The 54th target gene is the hsa-miR-3185 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0363] The 55th target gene is the hsa-miR-642b-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0364] The 56th target gene is the hsa-miR-1249 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0365] The 57th target gene is the hsa-miR-744-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0366] The 58th target gene is the hsa-miR-4442 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0367] The 59th target gene is the hsa-miR-1228-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0368] The 60th target gene is the hsa-miR-939-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0369] The 61st target gene is the hsa-miR-6845-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0370] The 62nd target gene is the hsa-miR-887-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0371] The 63rd target gene is the hsa-miR-7845-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0372] The 64th target gene is the hsa-miR-6729-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0373] The 65th target gene is the hsa-miR-4632-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0374] The 66th target gene is the hsa-miR-615-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0375] The 67th target gene is the hsa-miR-6724-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0376] The 68th target gene is the hsa-miR-4728-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0377] The 69th target gene is the hsa-miR-6732-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0378] The 70th target gene is the hsa-miR-6816-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0379] The 71st target gene is the hsa-miR-4695-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0380] The 72nd target gene is the hsa-miR-6088 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0381] The 73rd target gene is the hsa-miR-7975 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0382] The 74th target gene is the hsa-miR-3197 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0383] The 75th target gene is the hsa-miR-6125 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0384] The 76th target gene is the hsa-miR-4433-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0385] The 77th target gene is the hsa-miR-6727-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0386] The 78th target gene is the hsa-miR-4706 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0387] The 79th target gene is the hsa-miR-7847-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0388] The 80th target gene is the hsa-miR-6805-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0389] The 81st target gene is the hsa-miR-6766-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0390] The 82nd target gene is the hsa-miR-1913 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0391] The 83rd target gene is the hsa-miR-4649-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0392] The 84th target gene is the hsa-miR-602 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0393] The 85th target gene is the hsa-miR-3663-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0394] The 86th target gene is the hsa-miR-6893-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0395] The 87th target gene is the hsa-miR-6861-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0396] The 88th target gene is the hsa-miR-4449 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0397] The 89th target gene is the hsa-miR-6842-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0398] The 90th target gene is the hsa-miR-4454 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0399] The 91st target gene is the hsa-miR-5195-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0400] The 92nd target gene is the hsa-miR-663b gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0401] The 93rd target gene is the hsa-miR-6765-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0402] The 94th target gene is the hsa-miR-4513 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0403] The 95th target gene is the hsa-miR-614 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0404] The 96th target gene is the hsa-miR-6785-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0405] The 97th target gene is the hsa-miR-6777-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0406] The 98th target gene is the hsa-miR-940 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0407] The 99th target gene is the hsa-miR-4741 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0408] The 100th target gene is the hsa-miR-6870-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0409] The 101st target gene is the hsa-miR-6131 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0410] The 102nd target gene is the hsa-miR-150-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0411] The 103rd target gene is the hsa-miR-4707-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0412] The 104th target gene is the hsa-miR-1915-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0413] The 105th target gene is the hsa-miR-3937 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0414] The 106th target gene is the hsa-miR-937-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0415] The 107th target gene is the hsa-miR-4443 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0416] The 108th target gene is the hsa-miR-1914-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0417] The 109th target gene is the hsa-miR-3620-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0418] The 110th target gene is the hsa-miR-1268b gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0419] The 111th target gene is the hsa-miR-1227-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0420] The 112th target gene is the hsa-miR-6880-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0421] The 113th target gene is the hsa-miR-4417 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0422] The 114th target gene is the hsa-miR-6802-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0423] The 115th target gene is the hsa-miR-6769a-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0424] The 116th target gene is the hsa-miR-663a gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0425] The 117th target gene is the hsa-miR-6721-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0426] The 118th target gene is the hsa-miR-4532 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0427] The 119th target gene is the hsa-miR-7977 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0428] The 120th target gene is the hsa-miR-92b-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0429] The 121st target gene is the hsa-miR-371a-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0430] The 122nd target gene is the hsa-miR-6126 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0431] The 123rd target gene is the hsa-miR-4734 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0432] The 124th target gene is the hsa-miR-4665-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0433] The 125th target gene is the hsa-miR-423-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0434] The 126th target gene is the hsa-miR-1469 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0435] The 127th target gene is the hsa-miR-4675 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0436] The 128th target gene is the hsa-miR-1915-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0437] The 129th target gene is the hsa-miR-6716-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0438] The 130th target gene is the hsa-miR-718 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0439] The 131st target gene is the hsa-miR-4281 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0440] The 132nd target gene is the hsa-miR-6820-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0441] The 133rd target gene is the hsa-miR-6795-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0442] The 134th target gene is the hsa-miR-6779-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0443] The 135th target gene is the hsa-miR-7109-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0444] The 136th target gene is the hsa-miR-6798-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0445] The 137th target gene is the hsa-miR-4648 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0446] The 138th target gene is the hsa-miR-8059 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0447] The 139th target gene is the hsa-miR-6765-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0448] The 140th target gene is the hsa-miR-6132 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0449] The 141st target gene is the hsa-miR-4492 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0450] The 142nd target gene is the hsa-miR-7107-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0451] The 143rd target gene is the hsa-miR-3195 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0452] The 144th target gene is the hsa-miR-3180 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0453] The 145th target gene is the hsa-miR-296-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0454] The 146th target gene is the hsa-miR-564 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0455] The 147th target gene is the hsa-miR-1268a gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0456] The 148th target gene is the hsa-miR-6848-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0457] The 149th target gene is the hsa-miR-762 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0458] The 150th target gene is the hsa-miR-2861 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0459] The 151st target gene is the hsa-miR-1203 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0460] The 152nd target gene is the hsa-miR-1260b gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0461] The 153rd target gene is the hsa-miR-4476 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0462] The 154th target gene is the hsa-miR-6885-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0463] The 155th target gene is the hsa-miR-6769b-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0464] The 156th target gene is the hsa-miR-23b-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0465] The 157th target gene is the hsa-miR-1343-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0466] The 158th target gene is the hsa-miR-3621 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0467] The 159th target gene is the hsa-miR-4688 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0468] The 160th target gene is the hsa-miR-4286 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0469] The 161st target gene is the hsa-miR-4640-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0470] The 162nd target gene is the hsa-miR-4739 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0471] The 163rd target gene is the hsa-miR-1260a gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0472] The 164th target gene is the hsa-miR-4276 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0473] The 165th target gene is the hsa-miR-7106-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0474] The 166th target gene is the hsa-miR-128-2-5p gene, its homologs, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of the hsa-miR-128b (hsa-miR-128-2-3p) gene, which shares the same precursor as the miR-128b gene, or its transcription products, can be used as a marker for gastric cancer (Patent Document 2).
[0475] The 167th target gene is the hsa-miR-125a-3p gene, its homologs, its transcription products, or their mutants or derivatives. Previous reports have suggested that changes in the expression of this gene or its transcription products can be markers for gastric cancer (Patent Document 1).
[0476] The 168th target gene is the hsa-miR-92a-2-5p gene, its homologs, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of the hsa-miR-92-2 (hsa-miR-92a-2-3p) gene, which shares the same precursor as the miR-92a-2 gene, or its transcription products, can be a marker for gastric cancer (Patent Document 2).
[0477] The 169th target gene is the hsa-miR-486-3p gene, its homologs, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of the hsa-miR-486-5p gene, which shares the same precursor as the miR-486-3p gene, or its transcription products, can be a marker for gastric cancer (Patent Document 3).
[0478] The 170th target gene is the hsa-miR-3196 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0479] The 171st target gene is the hsa-miR-211-3p gene, its homologs, its transcription products, or their mutants or derivatives. Previous reports have suggested that changes in the expression of the hsa-miR-211 (hsa-miR-211-5p) gene, which shares the same precursor, or its transcription products, could be markers for gastric cancer (Patent Document 2).
[0480] The 172nd target gene is the hsa-miR-4271 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0481] The 173rd target gene is the hsa-miR-6851-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0482] The target gene of miR-174 is the hsa-miR-149-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0483] The 175th target gene is the hsa-miR-4667-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0484] The 176th target gene is the hsa-miR-135a-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0485] The 177th target gene is the hsa-miR-4486 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0486] The 178th target gene is the hsa-miR-4697-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0487] The 179th target gene is the hsa-miR-4725-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0488] The 180th target gene is the hsa-miR-6510-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0489] The 181st target gene is the hsa-miR-5001-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0490] The 182nd target gene is the hsa-miR-4673 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0491] The 183rd target gene is the hsa-miR-4466 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0492] The 184th target gene is the hsa-miR-23a-3p gene, its homologs, its transcription products, or their mutants or derivatives. Previous reports have suggested that changes in the expression of this gene or its transcription products can be markers for gastric cancer (Patent Document 2).
[0493] The 185th target gene is the hsa-miR-3656 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0494] The 186th target gene is the hsa-miR-6782-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0495] The 187th target gene is the hsa-miR-4689 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0496] The 188th target gene is the hsa-miR-451a gene, its homologs, its transcription products, or their mutants or derivatives. Previous reports have suggested that changes in the expression of this gene or its transcription products can be markers for gastric cancer (Patent Document 3).
[0497] The 189th target gene is the hsa-miR-4446-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0498] The 190th target gene is the hsa-miR-3180-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0499] The 191st target gene is the hsa-miR-642a-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0500] The 192nd target gene is the hsa-miR-6889-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0501] The 193rd target gene is the hsa-miR-3178 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0502] The 194th target gene is the hsa-miR-4665-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0503] The 195th target gene is the hsa-miR-6722-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0504] The 196th target gene is the hsa-miR-30c-1-3p gene, its homologs, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of the hsa-miR-30c (hsa-miR-30c-1-5p) gene, which shares the same precursor as the miR-30c gene, or its transcription products, can be used as a marker for gastric cancer (Patent Document 2).
[0505] The 197th target gene is the hsa-miR-4507 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products could be a marker for gastric cancer.
[0506] The 198th target gene is the hsa-miR-3141 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0507] The 199th target gene is the hsa-miR-1199-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of this gene or its transcription products can be a marker for gastric cancer.
[0508] The 200th target gene is the hsa-miR-6794-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for gastric cancer.
[0509] The 201st target gene is the hsa-miR-6774-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for gastric cancer.
[0510] The 202nd target gene is the hsa-miR-4707-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for gastric cancer.
[0511] The 203rd target gene is the hsa-miR-4534 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for gastric cancer.
[0512] The 204th target gene is the hsa-miR-4294 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for gastric cancer.
[0513] The 205th target gene is the hsa-miR-6850-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for gastric cancer.
[0514] The 206th target gene is the hsa-miR-6089 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for gastric cancer.
[0515] The 207th target gene is the hsa-miR-671-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for gastric cancer.
[0516] 2. Nucleic acid probes or primers for detecting gastric cancer In the present invention, the nucleic acid capable of specifically binding to the target nucleic acid as the stomach cancer marker can be used as a nucleic acid for detecting or diagnosing stomach cancer, such as a nucleic acid probe or primer.
[0517] In the present invention, nucleic acid probes or primers that can be used to detect or diagnose gastric cancer include target nucleic acids as the above-mentioned gastric cancer markers, such as human-derived hsa-miR-4257, hsa-miR-6726-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-6787-5p, hsa-miR-6875-5p, hsa-miR-1225-3p, hsa-miR-8063, hsa-miR-6781-5p, hsa-miR-4746-3p, and hsa-miR-19. 08-5p, hsa-miR-6756-5p, hsa-miR-204-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-6825-5p, hsa-miR-7108-5p, hsa-miR-4792, hsa-miR-7641 , hsa-miR-3188, hsa-miR-3131, hsa-miR-6780b-5p, hsa-miR-8069, hsa-miR-6840-3p, hsa-miR-8072, hsa-miR-1233-5p, hsa-miR-6887-5p, hsa-mi R-1231, hsa-miR-5572, hsa-miR-6738-5p, hsa-miR-6784-5p, hsa-miR-6791-5p, hsa-miR-6749-5p, hsa-miR-6741-5p, hsa-miR-128-1-5p, hsa-mi R-4419b, hsa-miR-6746-5p, hsa-miR-3184-5p, hsa-miR-3679-5p, hsa-miR-7110-5p, hsa-miR-4516, hsa-miR-6717-5p, hsa-miR-6826-5p, hsa-mi R-4433b-3p, hsa-miR-3679-3p, hsa-miR-3135b, hsa-miR-3622a-5p, hsa-miR-711, hsa-miR-4467, hsa-miR-6857-5p, hsa-miR-6515-3p, hsa-miR- 1225-5p, hsa-miR-187-5p, hsa-miR-3185, hsa-miR-642b-3p, hsa-miR-1249, hsa-miR-744-5p, hsa-miR-4442, hsa-miR-1228-3p, hsa-miR-939-5p,hsa-miR-6845-5p, hsa-miR-887-3p, hsa-miR-7845-5p, hsa-miR-6729-5p, hsa-miR-4632-5p, hsa-miR-615-5p, hsa-miR-6724-5p, hsa-miR-4728-5p, hsa-miR-6732-5p, hsa-miR-6816-5p, hsa-miR-4695-5p, hsa-miR-6088, hsa-miR-7975, hsa-miR-3197, hsa-miR-6125, hsa-miR-4433-3p, hsa- miR-6727-5p, hsa-miR-4706, hsa-miR-7847-3p, hsa-miR-6805-3p, hsa-miR-6766-3p, hsa-miR-1913, hsa-miR-4649-5p, hsa-miR-602, hsa-miR-3 663-3p, hsa-miR-6893-5p, hsa-miR-6861-5p, hsa-miR-4449, hsa-miR-6842-5p, hsa-miR-4454, hsa-miR-5195-3p, hsa-miR-663b, hsa-miR-6765-5 p, hsa-miR-4513, hsa-miR-614, hsa-miR-6785-5p, hsa-miR-6777-5p, hsa-miR-940, hsa-miR-4741, hsa-miR-6870-5p, hsa-miR-6131, hsa-miR-15 0-3p, hsa-miR-4707-5p, hsa-miR-1915-3p, hsa-miR-3937, hsa-miR-937-5p, hsa-miR-4443, hsa-miR-1914-3p, hsa-miR-3620-5p, hsa-miR-1268b hsa-miR-1227-5p, hsa-miR-6880-5p, hsa-miR-4417, hsa-miR-6802-5p, hsa-miR-6769a-5p, hsa-miR-663a, hsa-miR-6721-5p, hsa-miR-4532, hsa -miR-7977、hsa-miR-92b-5p、hsa-miR-371a-5p、hsa-miR-6126、hsa-miR-4734、hsa-miR-4665-3p、hsa-miR-423-5p、hsa-miR-1469、hsa-miR-4675、hsa-miR-1915-5p, hsa-miR-6716-5p, hsa-miR-718, hsa-miR-4281, hsa-miR-6820-5p, hsa-miR-6795-5p, hsa-miR-6779-5p, hsa-miR-7109-5p, hs a-miR-6798-5p, hsa-miR-4648, hsa-miR-8059, hsa-miR-6765-3p, hsa-miR-6132, hsa-miR-4492, hsa-miR-7107-5p, hsa-miR-3195, hsa-miR-3180, hsa-miR-296-3p, hsa-miR-564, hsa-miR-1268a, hsa-miR-6848-5p, hsa-miR-762, hsa-miR-2861, hsa-miR-1203, hsa-miR-1260b, hsa-miR-4476, h sa-miR-6885-5p, hsa-miR-6769b-5p, hsa-miR-23b-3p, hsa-miR-1343-5p, hsa-miR-3621, hsa-miR-4688, hsa-miR-4286, hsa-miR-4640-5p, hsa-mi hsa-miR-4739, hsa-miR-1260a, hsa-miR-4276, hsa-miR-7106, hsa-miR-6794-5p, hsa-miR-6774-5p, hsa-miR-4707-3p, hsa-miR-4534, hsa-miR-4294, hsa-miR-6850-5p, hsa-miR-6089 or hsa-miR-671-5p, or combinations thereof, or homologues thereof, transcription products thereof, variants or derivatives thereof, and hsa-miR- 128-2-5p, hsa-miR-125a-3p, hsa-miR-92a-2-5p or hsa-miR-486-3p, or combinations thereof, or homologues thereof, transcription products thereof, variants or derivatives thereof, as well as hsa-miR-3196, hsa-miR-211-3p, hsa-miR-4271, hsa-miR-6851-5p, hsa-miR-149-3p, hsa-miR-4667-5p, hsa-miR-135a-3p, hsa-miR-4486, optionally in combination therewith.hsa-miR-4697-5p, hsa-miR-4725-3p, hsa-miR-6510-5p, hsa-miR-5001-5p, hsa-miR-4673, hsa-miR-4466, hsa-miR-23a-3 p, hsa-miR-3656, hsa-miR-6782-5p, hsa-miR-4689, hsa-miR-451a, hsa-miR-4446-3p, hsa-miR-3180-3p, hsa-miR-642a-3 The present invention enables qualitative and / or quantitative measurement of the presence, expression level or abundance of miR-6889-5p, hsa-miR-3178, hsa-miR-4665-5p, hsa-miR-6722-3p, hsa-miR-30c-1-3p, hsa-miR-4507, hsa-miR-3141 or hsa-miR-1199-5p, or combinations thereof, or their homologs, transcription products, variants or derivatives thereof.
[0518] The expression levels of some of the above target nucleic acids may be increased or decreased in subjects with gastric cancer compared to healthy subjects, depending on the type of target nucleic acid (hereinafter referred to as "increase / decrease"). Therefore, the nucleic acids of the present invention can be effectively used to detect gastric cancer by measuring the expression levels of the above target nucleic acids in body fluids derived from subjects (e.g., humans) suspected of having gastric cancer and body fluids derived from healthy subjects, and comparing the results.
[0519] The nucleic acid probe or primer that can be used in the present invention is a nucleic acid probe that can specifically bind to at least one of the polynucleotides consisting of the base sequences represented by SEQ ID NOs: 1 to 165 and 635 to 642, or a primer for amplifying at least one of the polynucleotides consisting of the base sequences represented by SEQ ID NOs: 1 to 165 and 635 to 642.
[0520] Nucleic acid probes or primers that can be used in the present invention may further include a nucleic acid probe capable of specifically binding to at least one polynucleotide consisting of the base sequence represented by SEQ ID NOs: 166 to 169, or a primer for amplifying at least one polynucleotide consisting of the base sequence represented by SEQ ID NOs: 166 to 169.
[0521] The nucleic acid probe or primer usable in the present invention may further include a nucleic acid probe capable of specifically binding to at least one polynucleotide consisting of the base sequence represented by SEQ ID NOs: 170 to 199, or a primer for amplifying at least one polynucleotide consisting of the base sequence represented by SEQ ID NOs: 170 to 199.
[0522] Specifically, the nucleic acid probe or primer includes a combination of one or more polynucleotides selected from a group of polynucleotides containing a base sequence represented by any one of SEQ ID NOs: 1 to 657, or a base sequence in which u is replaced by t, and complementary polynucleotides thereto, a group of polynucleotides hybridizing under stringent conditions (described below) with DNA consisting of a base sequence complementary to the base sequence, and complementary polynucleotides thereto, and a group of polynucleotides containing 15 or more, preferably 17 or more, consecutive bases in the base sequence of the polynucleotide group. These polynucleotides can be used as nucleic acid probes and primers for detecting the above-mentioned gastric cancer markers, which are target nucleic acids.
[0523] More specifically, examples of nucleic acid probes or primers that can be used in the present invention are one or more polynucleotides selected from the group consisting of any of the following polynucleotides (a) to (e): (a) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a nucleotide sequence in which u is t in the nucleotide sequence, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides; (b) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642; (c) a polynucleotide consisting of a base sequence complementary to any of the base sequences represented by SEQ ID NOs: 1 to 165 and 635 to 642, or the base sequence in which u is t, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a base sequence in which u is t in the base sequence; and (e) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d).
[0524] The nucleic acid probe or primer usable in the present invention can further comprise, in addition to at least one polynucleotide selected from the group consisting of the above-mentioned polynucleotides (a) to (e), a polynucleotide selected from the group consisting of the polynucleotides shown in (f) to (j) below. (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 166 to 169 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 166 to 169; (h) a polynucleotide comprising a nucleotide sequence complementary to any one of SEQ ID NOs: 166 to 169, or a nucleotide sequence in which u is t in the nucleotide sequence, or a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides; (i) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 166 to 169, or a base sequence in which u is t in the base sequence; and (j) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i).
[0525] The nucleic acid probe or primer usable in the present invention can further comprise, in addition to at least one polynucleotide selected from the group consisting of the above-mentioned polynucleotides (a) to (j), a polynucleotide selected from the group consisting of the polynucleotides shown in (k) to (o) below. (k) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 170 to 199 or a base sequence in which u is t in the base sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 170 to 199; (m) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any one of SEQ ID NOs: 170 to 199, or a nucleotide sequence in which u is t in the nucleotide sequence; a variant thereof; a derivative thereof; or a fragment thereof comprising 15 or more consecutive nucleotides; (n) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 170 to 199, or a base sequence in which u is t in the base sequence; and (o) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (k) to (n).
[0526] In the above polynucleotides, the "fragment containing 15 or more consecutive bases" may include, but is not limited to, a number of consecutive bases in the base sequence of each polynucleotide, such as 15 to less than the total number of bases in the sequence, 17 to less than the total number of bases in the sequence, or 19 to less than the total number of bases in the sequence.
[0527] The above polynucleotides or fragments thereof used in the present invention may be either DNA or RNA.
[0528] The above-mentioned polynucleotides that can be used in the present invention can be prepared using common techniques such as DNA recombinant technology, PCR, and methods using automated DNA / RNA synthesizers.
[0529] The DNA recombinant DNA technology and PCR method can be described, for example, in Ausubel et al., Current Protocols in Molecular Biology, John Willey & Sons, US (1993); Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, US (1989).
[0530] Human-derived hsa-miR-4257, hsa-miR-6726-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-6787-5p, hsa-miR-6875-5p, hsa-miR-1225-3p, hsa-miR-8063, hsa-miR-6781-5p, hsa-miR-4746-3p, hsa-miR-1908-5p, hsa-miR-6756-5p, hsa-miR-204-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-6825-5p, hsa-miR-7108-5p, hsa-miR-4792, hsa-miR-7641, hsa-miR-3188, hsa-miR-3131, hsa-miR-6780b-5p, hsa-miR-8069, hsa-miR-6840-3p, hsa-miR-8072, hsa-miR-1233-5p, hsa-miR-6887-5p, hsa-miR-1231, hsa-miR-5572, hsa-miR-6738-5p, hsa-miR-6784-5p, hsa-miR-6791-5p, hsa-miR-6749-5p, hsa-miR-6741-5p, hsa-miR-128-1-5p, hsa-miR-4419b, hsa-miR-6746-5p, hsa-miR-3184-5p, hsa-miR-3679-5p, hsa-miR-7110-hsa-miR-4632-5p, hsa-miR-615-5p, hsa-miR-6724-5p, hsa-miR-4728-5p, hsa-miR-6732-5p, hsa-miR-6816-5p, hsa-miR-4695-5p, hsa-miR-6088 hsa-miR-7975, hsa-miR-3197, hsa-miR-6125, hsa-miR-4433-3p, hsa-miR-6727-5p, hsa-miR-4706, hsa-miR-7847-3p, hsa-miR-6805-3p, hsa-miR-6 766-3p, hsa-miR-1913, hsa-miR-4649-5p, hsa-miR-602, hsa-miR-3663-3p, hsa-miR-6893-5p, hsa-miR-6861-5p, hsa-miR-4449, hsa-miR-6842-5p hsa-miR-4454 hsa-miR-5195-3p hsa-miR-663b hsa-miR-6765-5p hsa-miR-4513 hsa-miR-614 hsa-miR-6785-5p hsa-miR-6777-5p hsa-miR-9 40, hsa-miR-4741, hsa-miR-6870-5p, hsa-miR-6131, hsa-miR-150-3p, hsa-miR-4707-5p, hsa-miR-1915-3p, hsa-miR-3937, hsa-miR-937-5p, hsa- miR-4443, hsa-miR-1914-3p, hsa-miR-3620-5p, hsa-miR-1268b, hsa-miR-1227-5p, hsa-miR-6880-5p, hsa-miR-4417, hsa-miR-6802-5p, hsa-miR-6 769a-5p、hsa-miR-663a、hsa-miR-6721-5p、hsa-miR-4532、hsa-miR-7977 、hsa-miR-92b-5p、hsa-miR-371a-5p、hsa-miR-6126、hsa-miR-4734、hsa-m iR-4665-3p, hsa-miR-423-5p, hsa-miR-1469, hsa-miR-4675, hsa-miR-1915-5p, hsa-miR-6716-5p, hsa-miR-718, hsa-miR-4281, hsa-miR-6820-5phsa-miR-6795-5p, hsa-miR-6779-5p, hsa-miR-7109-5p, hsa-miR-6798-5p, hsa-miR-4648, hsa-miR-8059, hsa-miR-6765-3p, hsa-miR-6132, hsa-miR-4492, hsa-miR-7107-5p, hsa-miR-3195, hsa-miR-3180, hsa-miR-296-3p, hsa-miR-564, hsa-miR-1268a, hsa-miR-6848-5p, hsa-miR-762, hsa-miR-2861, hsa-miR-1203, hsa-miR-1260b, hsa-miR-4476, hsa-miR-6885-5p, hsa-miR-6769b-5p, hsa-miR-23b-3p, hsa-miR-1343-5p, hsa-miR-3621, hsa-miR-4688, hsa-miR-4286, hsa-miR-4640-5p, hsa-miR-4739, hsa-miR-1260a, hsa-miR-4276, hsa-miR-7106, hsa-miR-6794-5p, hsa-miR-6774-5p, hsa-miR-4707-3p, hsa-miR-4534, hsa-miR-4294, hsa-miR-6850-5p, hsa-miR-6089, and hsa-miR-671-5p, hsa-miR-128-2-5p, hsa-miR-125a-3p, hsa-miR-92a-2-5p, hsa-miR-486-3p, hsa-miR-3196, hsa-miR-211-3p, hsa-miR-4271, hsa-miR-6851-5p, hsa-miR-149-3p, hsa-miR-4667-5p, hsa-miR-135a-3p, hsa-miR-4486, hsa-miR-4697-5p, hsa-miR-4725-3p, hsa-miR-6510-5p, hsa-miR-5001-5p, hsa-miR-4673, hsa-miR-4466, hsa-miR-23a-3p, hsa-miR-3656, hsa-miR-6782-5p, hsa-miR-4689, hsa-miR-451a, hsa-miR-4446-3p, hsa-miR-3180-3p, hsa-miR-642a-3p, hsa-miR-6889-5phsa-miR-3178, hsa-miR-4665-5p, hsa-miR-6722-3p, hsa-miR-30c-1-3p, hsa-miR-4507, hsa-miR-3141, and hsa-miR-1199-5p are known, and as mentioned above, methods for obtaining them are also known. Therefore, by cloning these genes, polynucleotides usable as nucleic acid probes or primers in the present invention can be prepared.
[0531] Such nucleic acid probes or primers can be chemically synthesized using an automated DNA synthesizer. The phosphoramidite method is generally used for this synthesis, and this method allows automated synthesis of single-stranded DNA up to about 100 bases. Automated DNA synthesizers are commercially available from, for example, Polygen, ABI, and Applied BioSystems.
[0532] Alternatively, the polynucleotides of the present invention can be prepared by cDNA cloning techniques, such as the microRNA Cloning Kit Wako.
[0533] Here, the sequences of nucleic acid probes and primers for detecting polynucleotides consisting of the nucleotide sequences represented by any of SEQ ID NOS: 1 to 199 and 635 to 642 do not exist in vivo as miRNAs or their precursors. For example, the nucleotide sequences represented by SEQ ID NOS: 7 and 52 are generated from a precursor represented by SEQ ID NOS: 206, but this precursor has a hairpin-like structure as shown in FIG. 1, and the nucleotide sequences represented by SEQ ID NOS: 7 and 52 have mismatched sequences with each other. Therefore, a nucleotide sequence completely complementary to the nucleotide sequence represented by SEQ ID NOS: 7 or 52 is not naturally generated in vivo. Therefore, nucleic acid probes and primers for detecting the nucleotide sequences represented by any of SEQ ID NOS: 1 to 199 and 635 to 642 have artificial nucleotide sequences that do not exist in vivo.
[0534] 3. Gastric cancer detection kit or device The present invention also provides a kit or device for detecting stomach cancer, which comprises one or more polynucleotides (which may include mutants, fragments, or derivatives; hereinafter, sometimes referred to as detection polynucleotides) that can be used as nucleic acid probes or primers in the present invention for measuring a target nucleic acid that is a stomach cancer marker.
[0535] The target nucleic acid that is a gastric cancer marker in the present invention is selected from the following Group 1: miR-4257, miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5 p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8 069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741- 5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3 679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249 miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p miR-4728-5p miR-6732-5p miR-6816-5p miR-4695-5p miR-6088 miR-7975 miR-3197 miR-6125 miR-4433-3p miR-6727-5p miR-4706 miR-78 47-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-122 7-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR- 6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-44 76, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089, miR-671-5p.
[0536] Additional target nucleic acids that may be optionally further measured are preferably selected from the following Group 2: miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, and miR-486-3p. Additional target nucleic acids that may be optionally further measured are preferably selected from the following Group 3: miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, and miR-4673. , miR-4466, miR-23a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a -3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141 and miR-1199-5p.
[0537] The kit or device of the present invention comprises a nucleic acid capable of specifically binding to the target nucleic acid that is the above-mentioned gastric cancer marker, preferably the nucleic acid probe or primer described in 2 above, specifically one or more polynucleotides selected from the polynucleotides described in 2 above or their mutants, etc.
[0538] Specifically, the kit or device of the present invention may comprise at least one of a polynucleotide containing (or consisting of) a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a base sequence in which u is t in the base sequence, a polynucleotide containing (or consisting of) a complementary sequence thereof, a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a mutant or fragment containing 15 or more consecutive bases of these polynucleotide sequences.
[0539] The kit or device of the present invention may further comprise one or more polynucleotides containing (or consisting of) a base sequence represented by any one of SEQ ID NOs: 166 to 169, or a base sequence in which u is t in said base sequence, a polynucleotide containing (or consisting of) a complementary sequence thereof, a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a mutant or fragment containing 15 or more consecutive bases of these polynucleotide sequences.
[0540] The kit or device of the present invention may further comprise one or more of a polynucleotide containing (or consisting of) a base sequence represented by any one of SEQ ID NOs: 170 to 199, or a base sequence in which u is t in said base sequence, a polynucleotide containing (or consisting of) a complementary sequence thereof, a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a mutant or fragment containing 15 or more consecutive bases of these polynucleotide sequences.
[0541] The fragment that can be contained in the kit or device of the present invention is, for example, one or more, preferably two or more, polynucleotides selected from the group consisting of the following (1) to (3): (1) A polynucleotide comprising 15 or more consecutive bases in a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642 in which u is t, or a complementary sequence thereof. (2) A polynucleotide comprising 15 or more consecutive bases in a base sequence represented by any one of SEQ ID NOs: 166 to 169 in which u is t, or a complementary sequence thereof. (3) A polynucleotide comprising 15 or more consecutive bases in a base sequence represented by any one of SEQ ID NOs: 170 to 199 in which u is t, or a complementary sequence thereof.
[0542] In a preferred embodiment, the polynucleotide is a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a base sequence in which u is t in the base sequence; a polynucleotide consisting of a complementary sequence thereof; a polynucleotide that hybridizes to such a polynucleotide under stringent conditions; or a variant thereof containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.
[0543] In a preferred embodiment, the polynucleotide is a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 166 to 169, or a base sequence in which u is t in the base sequence, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a variant thereof containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.
[0544] In a preferred embodiment, the polynucleotide is a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 170 to 199, or a base sequence in which u is t in the base sequence, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a variant thereof containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.
[0545] In a preferred embodiment, the fragment may be a polynucleotide containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.
[0546] In the present invention, the size of a polynucleotide fragment is, for example, the number of consecutive bases in the base sequence of each polynucleotide, ranging from 15 to less than the total number of bases in the sequence, from 17 to less than the total number of bases in the sequence, or from 19 to less than the total number of bases in the sequence.
[0547] Specific examples of the above-mentioned combinations of polynucleotides as target nucleic acids in the kit or device of the present invention include combinations of polynucleotides consisting of any of the base sequences represented by the sequence numbers shown in Table 1 (SEQ ID NOS: 1 to 199 and 635 to 642, which correspond to the miRNA markers in Table 1), but these are merely examples, and all other possible combinations are intended to be encompassed by the present invention.
[0548] For example, in the present invention, a combination of target nucleic acids in a kit or device for distinguishing between stomach cancer patients and healthy subjects is preferably a combination of two or more of the above-mentioned polynucleotides consisting of a base sequence represented by any of the sequence numbers shown in Table 1, and usually a combination of two can provide sufficient performance.
[0549] Specifically, as a combination of two polynucleotides consisting of a base sequence or a complementary sequence thereof for distinguishing between gastric cancer patients and healthy subjects, among the combinations of two polynucleotides consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 199 and 635 to 642, a combination containing at least one polynucleotide consisting of a newly discovered base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642 is preferred.
[0550] Furthermore, preferred combinations of cancer-specific polynucleotides that can distinguish gastric cancer patients from not only healthy subjects but also other cancer patients include, for example, multiple combinations of at least one polynucleotide selected from the group consisting of polynucleotides of SEQ ID NOs: 9, 13, 21, 27, 34, 36, 66, 75, 95, 98, 108, 130, 135, 143, 155, 183, 185, 187, 191, 193, 194, 635, 636, 637, 638, 639, 640, 641, and 642 (hereinafter, this group will be referred to as "cancer-specific polynucleotide group 1") with polynucleotides of other SEQ ID NOs.
[0551] Furthermore, as a combination of cancer type-specific polynucleotides that can distinguish gastric cancer patients from not only healthy subjects but also other cancer patients, a combination of multiple polynucleotides selected from Cancer Type-Specific Polynucleotide Group 1 is more preferable.
[0552] Furthermore, as a combination of cancer type-specific polynucleotides that can distinguish gastric cancer patients from not only healthy subjects but also other cancer patients, a combination of multiple polynucleotides selected from cancer type-specific polynucleotide group 1 that includes at least one polynucleotide selected from the group consisting of polynucleotides of SEQ ID NOs: 21, 34, 36, 98, and 155 included in cancer type-specific polynucleotide group 1 (hereinafter, this group will be referred to as "cancer type-specific polynucleotide group 2").
[0553] The number of combinations of the above-mentioned cancer type-specific polynucleotides can be 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, but combinations of 6 or more are more preferred, and usually, a combination of 6 can provide sufficient performance.
[0554] Non-limiting examples of combinations of a polynucleotide consisting of the base sequence shown in SEQ ID NO: 21 or its complementary sequence with a polynucleotide consisting of the base sequences shown in the SEQ ID NOs of five polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences are shown below. (1) Combination of SEQ ID NOs: 9, 21, 36, 98, 130, 637 (markers: hsa-miR-6781-5p, hsa-miR-3131, hsa-miR-4419b, hsa-miR-940, hsa-miR-718, hsa-miR-4707-3p) (2) Combination of SEQ ID NOs: 9, 21, 34, 36, 98, 637 (markers: hsa-miR-6781-5p, hsa-miR-3131, hsa-miR-6741-5p, hsa-miR-4419b, hsa-miR-940, hsa-miR-4707-3p) (3) Combinations of SEQ ID NOs: 9, 21, 34, 36, 98, and 155 (markers: hsa-miR-6781-5p, hsa-miR-3131, hsa-miR-6741-5p, hsa-miR-4419b, hsa-miR-940, and hsa-miR-6769b-5p) (4) Combinations of SEQ ID NOs: 21, 36, 75, 98, 155, and 635 (markers: hsa-miR-3131, hsa-miR-4419b, hsa-miR-6125, hsa-miR-940, hsa-miR-6769b-5p, and hsa-miR-6794-5p) (5) Combinations of SEQ ID NOs: 9, 21, 36, 98, 108, and 155 (markers: hsa-miR-6781-5p, hsa-miR-3131, hsa-miR-4419b, hsa-miR-940, hsa-miR-1914-3p, and hsa-miR-6769b-5p)
[0555] Further, non-limiting examples include combinations of a polynucleotide consisting of the base sequence shown in SEQ ID NO: 34 or its complementary sequence with polynucleotides consisting of the base sequences shown in the SEQ ID NOs of five polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences. (1) Combinations of SEQ ID NOs: 34, 36, 143, 155, 187, and 635 (markers: hsa-miR-6741-5p, hsa-miR-4419b, hsa-miR-3195, hsa-miR-6769b-5p, hsa-miR-4689, and hsa-miR-6794-5p) (2) Combinations of SEQ ID NOs: 9, 34, 36, 66, 98, 187 (markers: hsa-miR-6781-5p, hsa-miR-6741-5p, hsa-miR-4419b, hsa-miR-615-5p, hsa-miR-940, hsa-miR-4689) (3) Combinations of SEQ ID NOs: 9, 34, 36, 98, 187, and 637 (markers: hsa-miR-6781-5p, hsa-miR-6741-5p, hsa-miR-4419b, hsa-miR-940, hsa-miR-4689, and hsa-miR-4707-3p) (4) Combinations of SEQ ID NOs: 9, 34, 36, 98, 185, and 637 (markers: hsa-miR-6781-5p, hsa-miR-6741-5p, hsa-miR-4419b, hsa-miR-940, hsa-miR-3656, and hsa-miR-4707-3p) (5) Combinations of SEQ ID NOs: 9, 34, 36, 98, 637, and 639 (markers: hsa-miR-6781-5p, hsa-miR-6741-5p, hsa-miR-4419b, hsa-miR-940, hsa-miR-4707-3p, and hsa-miR-4294)
[0556] Further, non-limiting examples include combinations of a polynucleotide consisting of the base sequence shown in SEQ ID NO: 36 or its complementary sequence with polynucleotides consisting of the base sequences shown in the SEQ ID NOs of five polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences. (1) Combinations of SEQ ID NOs: 9, 36, 98, 108, 638, and 639 (markers: hsa-miR-6781-5p, hsa-miR-4419b, hsa-miR-940, hsa-miR-1914-3p, hsa-miR-4534, and hsa-miR-4294) (2) Combinations of SEQ ID NOs: 36, 98, 155, 194, 635, and 642 (markers: hsa-miR-4419b, hsa-miR-940, hsa-miR-6769b-5p, hsa-miR-4665-5p, hsa-miR-6794-5p, and hsa-miR-671-5p) (3) Combinations of SEQ ID NOs: 9, 34, 36, 75, 98, and 637 (markers: hsa-miR-6781-5p, hsa-miR-6741-5p, hsa-miR-4419b, hsa-miR-6125, hsa-miR-940, and hsa-miR-4707-3p) (4) Combinations of SEQ ID NOs: 21, 36, 98, 155, 185, and 635 (markers: hsa-miR-3131, hsa-miR-4419b, hsa-miR-940, hsa-miR-6769b-5p, hsa-miR-3656, and hsa-miR-6794-5p) (5) Combinations of SEQ ID NOs: 9, 36, 98, 108, 155, and 635 (markers: hsa-miR-6781-5p, hsa-miR-4419b, hsa-miR-940, hsa-miR-1914-3p, hsa-miR-6769b-5p, and hsa-miR-6794-5p)
[0557] Further, non-limiting examples include combinations of a polynucleotide consisting of the base sequence shown in SEQ ID NO: 98 or its complementary sequence with polynucleotides consisting of the base sequences shown in the SEQ ID NOs of five polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences. (1) Combinations of SEQ ID NOs: 9, 36, 98, 130, 194, and 637 (markers: hsa-miR-6781-5p, hsa-miR-4419b, hsa-miR-940, hsa-miR-718, hsa-miR-4665-5p, and hsa-miR-4707-3p) (2) Combinations of SEQ ID NOs: 21, 36, 98, 108, 155, and 635 (markers: hsa-miR-3131, hsa-miR-4419b, hsa-miR-940, hsa-miR-1914-3p, hsa-miR-6769b-5p, and hsa-miR-6794-5p) (3) Combinations of SEQ ID NOs: 9, 36, 98, 108, 155, and 639 (markers: hsa-miR-6781-5p, hsa-miR-4419b, hsa-miR-940, hsa-miR-1914-3p, hsa-miR-6769b-5p, and hsa-miR-4294) (4) Combinations of SEQ ID NOs: 9, 36, 98, 155, 187, and 639 (markers: hsa-miR-6781-5p, hsa-miR-4419b, hsa-miR-940, hsa-miR-6769b-5p, hsa-miR-4689, and hsa-miR-4294) (5) Combinations of SEQ ID NOs: 9, 36, 98, 155, 187, and 637 (markers: hsa-miR-6781-5p, hsa-miR-4419b, hsa-miR-940, hsa-miR-6769b-5p, hsa-miR-4689, and hsa-miR-4707-3p)
[0558] Further, non-limiting examples include combinations of a polynucleotide consisting of the nucleotide sequence shown in SEQ ID NO: 155 or its complementary sequence with polynucleotides consisting of the nucleotide sequences shown in the SEQ ID NOs of five polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences. (1) Combinations of SEQ ID NOs: 9, 36, 75, 98, 155, 635 (markers: hsa-miR-6781-5p, hsa-miR-4419b, hsa-miR-6125, hsa-miR-940, hsa-miR-6769b-5p, hsa-miR-6794-5p) (2) Combinations of SEQ ID NOs: 36, 98, 130, 155, 185, 635 (markers: hsa-miR-4419b, hsa-miR-940, hsa-miR-718, hsa-miR-6769b-5p, hsa-miR-3656, hsa-miR-6794-5p) (3) Combinations of SEQ ID NOs: 9, 13, 143, 155, 194, and 639 (markers: hsa-miR-6781-5p, hsa-miR-204-3p, hsa-miR-3195, hsa-miR-6769b-5p, hsa-miR-4665-5p, and hsa-miR-4294) (4) Combinations of SEQ ID NOs: 9, 13, 34, 36, 98, and 155 (markers: hsa-miR-6781-5p, hsa-miR-204-3p, hsa-miR-6741-5p, hsa-miR-4419b, hsa-miR-940, and hsa-miR-6769b-5p) (5) Combinations of SEQ ID NOs: 36, 98, 108, 155, 193, 635 (markers: hsa-miR-4419b, hsa-miR-940, hsa-miR-1914-3p, hsa-miR-6769b-5p, hsa-miR-3178, hsa-miR-6794-5p)
[0559] In addition to the polynucleotides of the present invention described above (which may include mutants, fragments, or derivatives), the kits or devices of the present invention may also include known polynucleotides or polynucleotides that will be discovered in the future that enable the detection of gastric cancer.
[0560] The kit of the present invention may contain, in addition to the polynucleotide of the present invention described above, and its variant or fragment thereof, antibodies for measuring known markers for gastric cancer testing, such as CEA and CA19-9.
[0561] The above-mentioned polynucleotides contained in the kit of the present invention may be packaged in different containers individually or in any combination.
[0562] The kit of the present invention may include a kit for extracting nucleic acid (for example, total RNA) from body fluids, cells, or tissues, a fluorescent labeling substance, an enzyme and medium for amplifying nucleic acid, instructions for use, and the like.
[0563] The device of the present invention is, for example, a device for measuring a cancer marker in which a nucleic acid such as the polynucleotide of the present invention described above is bound or attached to a solid phase. Examples of materials for the solid phase include plastic, paper, glass, and silicon, with plastic being a preferred solid phase material due to its ease of processing. The solid phase may have any shape, such as a square, round, strip, or film. The device of the present invention includes, for example, a device for measurement using hybridization techniques, and specific examples include a blotting device and a nucleic acid array (e.g., a microarray, a DNA chip, an RNA chip, etc.).
[0564] Nucleic acid array technology is a technique in which nucleic acids are spotted onto the surface of a solid phase that has been surface-treated as needed, such as by coating with L-lysine or by introducing functional groups such as amino or carboxyl groups, using a high-density dispenser called a spotter or arrayer, or by spraying nucleic acids onto the solid phase using an inkjet that ejects tiny droplets from a nozzle using a piezoelectric element, or by sequentially synthesizing nucleotides on the solid phase, to create an array such as a chip by binding or attaching the above nucleic acids one by one, and then using this array to measure target nucleic acids by utilizing hybridization.
[0565] The kits or devices of the present invention comprise nucleic acids capable of specifically binding to at least one or more, preferably at least two or more, more preferably at least three or more, and most preferably at least five or more to all of the polynucleotides of the miRNAs that are gastric cancer markers in Group 1. The kits or devices of the present invention may further comprise nucleic acids capable of specifically binding to at least one or more, preferably at least two or more, more preferably at least three or more, and most preferably at least five or more to all of the polynucleotides of the miRNAs that are gastric cancer markers in Group 2. The kits or devices of the present invention may further comprise nucleic acids capable of specifically binding to at least one or more, preferably at least two or more, more preferably at least three or more, and most preferably at least five or more to all of the polynucleotides of the miRNAs that are gastric cancer markers in Group 3.
[0566] The kit or device of the present invention can be used for the detection of the following four types of gastric cancer.
[0567] 4. Methods for detecting stomach cancer The present invention further relates to a method for detecting the presence or absence of the following groups in a sample using the kit or device of the present invention described in 3 above (containing the above-mentioned nucleic acid that can be used in the present invention): miR-4257, miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-682 ...204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-1225-3p, miR-1225-3p, miR-1225-3p, miR-1225-3p, miR-1225-3p, miR-1225-3p, miR-1225-3p, miR-1225-3p, miR-1225-3p R-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, mi R-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5 p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR- 887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-6088, m iR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602,The expression levels of genes derived from gastric cancer selected from miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-Expression levels of genes derived from gastric cancer selected from miR-92a-2-5p and miR-486-3p, and optionally the following group: miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23 a-3p, miR-3656, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141, and miR-1199-5p. The present invention provides a method for detecting stomach cancer, which comprises measuring the expression level of the gene in a sample of blood, serum, plasma, or other samples collected from a subject suspected of having stomach cancer and a healthy subject (including a non-stomach cancer patient), comparing the expression level of the gene in the sample with the control expression level in the healthy subject, and assessing the subject as having stomach cancer if there is a statistically significant difference in the expression level of the target nucleic acid in the sample.
[0568] The above-described method of the present invention enables early diagnosis of cancer with high sensitivity and specificity in a minimally invasive manner, thereby leading to early treatment and improved prognosis, and further enabling monitoring of disease progression and the effectiveness of surgical, radiotherapeutic, and chemotherapeutic treatments.
[0569] In the method of the present invention for extracting gastric cancer-derived genes from blood, serum, plasma, or other samples, it is particularly preferable to prepare the sample by adding the RNA extraction reagent in the 3D-Gene® RNA extraction reagent from liquid sample kit (Toray Industries, Inc.). However, the general acid phenol method (Acid Guanidinium-Phenol-Chloroform (AGPC) method) or Trizol® (Life Technologies) may also be used, or RNA extraction reagents containing acid phenol such as Trizol (Life Technologies) or Isogen (Nippon Gene) may also be used. Furthermore, kits such as the miRNeasy® Mini Kit (Qiagen) may also be used, but the method is not limited to these.
[0570] The present invention also provides use of the kit or device of the present invention for the in vitro detection of expression products of gastric cancer-derived miRNA genes in a specimen derived from a subject.
[0571] In the above-mentioned method of the present invention, the above-mentioned kit or device contains the polynucleotides usable in the present invention, either singly or in any possible combination, as explained above.
[0572] In the detection or (genetic) diagnosis of gastric cancer of the present invention, the polynucleotides contained in the kit or device of the present invention can be used as probes or primers. When used as primers, methods that can be used include, but are not limited to, TaqMan® MicroRNA Assays from Life Technologies and the miScript PCR System from Qiagen.
[0573] The polynucleotides contained in the kits or devices of the present invention can be used as primers or probes in known methods for specifically detecting specific genes, such as hybridization techniques such as Northern blotting, Southern blotting, in situ hybridization, Northern hybridization, and Southern hybridization, and quantitative amplification techniques such as quantitative RT-PCR. The sample to be measured is a body fluid, such as blood, serum, plasma, or urine, collected from the subject, depending on the type of detection method used. Alternatively, total RNA prepared from such body fluids by the above-mentioned methods may be used, or various polynucleotides, including cDNA, prepared from the RNA may be used.
[0574] The kit or device of the present invention is useful for diagnosing gastric cancer or detecting the presence or absence of gastric cancer. Specifically, gastric cancer detection using the kit or device can be performed by in vitro detection of the expression level of a gene detected by a nucleic acid probe or primer included in the kit or device using a sample such as blood, serum, plasma, or urine from a subject suspected of having gastric cancer. If the expression level of a target miRNA marker measured using a polynucleotide (including a mutant, fragment, or derivative thereof) consisting of at least one of the nucleotide sequences represented by SEQ ID NOs: 1 to 165 and 635 to 642 or their complementary sequences, and optionally one or more of the nucleotide sequences represented by SEQ ID NOs: 166 to 169 or their complementary sequences, and optionally one or more of the nucleotide sequences represented by SEQ ID NOs: 170 to 199 or their complementary sequences, in a sample such as blood, serum, plasma, or urine from a subject suspected of having gastric cancer is statistically significantly different from the expression level of the target miRNA marker in a sample such as blood, serum, plasma, or urine from a healthy subject, the subject can be evaluated as having gastric cancer.
[0575] The method of the present invention can be combined with imaging diagnostic methods such as gastric X-ray examination, gastroscopy, CT examination, PET examination, MRI examination, etc. The method of the present invention can specifically detect gastric cancer and can substantially distinguish gastric cancer from cancers other than gastric cancer.
[0576] A method for detecting whether a sample contains an expression product of a gene derived from gastric cancer or whether a sample contains an expression product of a gene derived from gastric cancer using the kit or device of the present invention involves collecting a body fluid such as blood, serum, plasma, or urine from a subject and measuring the expression level of a target gene contained therein using one or more polynucleotides (including mutants, fragments, or derivatives) selected from the group of polynucleotides of the present invention, thereby assessing the presence or absence of gastric cancer or detecting gastric cancer. The gastric cancer detection method of the present invention can also be used to evaluate or diagnose, for example, the presence or absence or degree of improvement of a gastric cancer patient when a therapeutic drug is administered to ameliorate the disease.
[0577] The method of the present invention includes, for example, the following steps (a), (b) and (c): (a) contacting a specimen from a subject in vitro with a polynucleotide in a kit or device of the present invention; (b) measuring the expression level of the target nucleic acid in a sample using the polynucleotide as a nucleic acid probe or primer; (c) assessing the presence or absence of stomach cancer (cells) in the subject based on the results of (b); may include:
[0578] Specifically, the present invention relates to miR-4257, miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-8063, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-miR-4454, miR-5195-3p, miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-466 5-3p, miR-423-5p, miR-1469, miR-4675, miR-1915-5p, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p , miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, m iR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, The expression level of a target nucleic acid in a specimen from a subject is measured using a nucleic acid capable of specifically binding to at least one or more, preferably at least two or more, polynucleotides selected from the group consisting of miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089, and miR-671-5p, and the measured expression level andand a control expression level measured in a similar manner in a healthy individual, and evaluating in vitro whether a subject is affected with or not affected with gastric cancer.
[0579] In this specification, "evaluation" refers to evaluation support based on the results of in vitro tests, rather than judgment by a doctor.
[0580] As described above, in a preferred embodiment of the method of the present invention, the target nucleic acids are specifically: miR-4257 is hsa-miR-4257; miR-6726-5p is hsa-miR-6726-5p; miR-1343-3p is hsa-miR-1343-3p; miR-1247-3p is hsa-miR-1247-3p; miR-6787-5p is hsa-miR-6787-5p; miR-6875-5p is hsa-miR-6875-5p; and miR-1225-3p is hsa-miR-1225-3p. , miR-8063 is hsa-miR-8063, miR-6781-5p is hsa-miR-6781-5p, miR-4746-3p is hsa-miR-4746-3p, miR-1908-5p is hsa-miR-1908-5p, miR-6756-5p is hsa-miR-6756-5p, miR-204-3p is hsa-miR-204-3p, miR-4651 is hsa-miR-4651, miR-6757-5p is hsa-miR-6757-5p, and miR-6825-5p is hsa-miR-4651. a-miR-6825-5p, miR-7108-5p is hsa-miR-7108-5p, miR-4792 is hsa-miR-4792, miR-7641 is hsa-miR-7641, miR-3188 is hsa-miR-3188, miR-3131 is hsa-miR-3131, miR-6780b-5p is hsa-miR-6780b-5p, miR-8069 is hsa-miR-8069, miR-6840-3p is hsa-miR-6840-3p, and miR-8072 is hsa -miR-8072, miR-1233-5p is hsa-miR-1233-5p, miR-6887-5p is hsa-miR-6887-5p, miR-1231 is hsa-miR-1231, miR-5572 is hsa-miR-5572, miR-6738-5p is hsa-miR-6738-5p, miR-6784-5p is hsa-miR-6784-5p, miR-6791-5p is hsa-miR-6791-5p, miR-6749-5p is hsa-miR-6749-5p,miR-6741-5p is hsa-miR-6741-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-4419b is hsa-miR-4419b, miR-6746-5p is hsa-miR-6746-5p, miR-3184-5p is hsa-miR-3184-5p, miR-3679-5p is hsa-miR-3679-5p, miR-7110-5p is hsa-miR-7110-5p, miR-4516 is hsa-miR-4516, and miR -6717-5p is hsa-miR-6717-5p, miR-6826-5p is hsa-miR-6826-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-3679-3p is hsa-miR-3679-3p, miR-3135b is hsa-miR-3135b, miR-3622a-5p is hsa-miR-3622a-5p, miR-711 is hsa-miR-711, miR-4467 is hsa-miR-4467, and miR-6857-5p is hsa-miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-1249, miR-744-5p, and miR-4442 are hsa-miR-4442. miR-1228-3p is hsa-miR-1228-3p, miR-939-5p is hsa-miR-939-5p, miR-6845-5p is hsa-miR-6845-5p, miR-887-3p is hsa-miR-887-3p, miR-7845-5p is hsa-miR-7845-5p, miR-6729-5p is hsa-miR-6729-5p, miR-4632-5p is hsa-miR-4632-5p, and miR-615-5p is hsa-miR-615-5p;miR-6724-5p is hsa-miR-6724-5p, miR-4728-5p is hsa-miR-4728-5p, miR-6732-5p is hsa-miR-6732-5p, miR-6816-5p is hsa-miR-6816-5p, miR-4695-5p is hsa-miR-4695-5p, miR-6088 is hsa-miR-6088, miR-7975 is hsa-miR-7975, miR-3197 is hsa-miR-3197, and miR-6125 is hsa-miR- 6125, miR-4433-3p is hsa-miR-4433-3p, miR-6727-5p is hsa-miR-6727-5p, miR-4706 is hsa-miR-4706, miR-7847-3p is hsa-miR-7847-3p, miR-6805-3p is hsa-miR-6805-3p, miR-6766-3p is hsa-miR-6766-3p, miR-1913 is hsa-miR-1913, miR-4649-5p is hsa-miR-4649-5p, and miR -602 is hsa-miR-602, miR-3663-3p is hsa-miR-3663-3p, miR-6893-5p is hsa-miR-6893-5p, miR-6861-5p is hsa-miR-6861-5p, miR-4449 is hsa-miR-4449, miR-6842-5p is hsa-miR-6842-5p, miR-4454 is hsa-miR-4454, miR-5195-3p is hsa-miR-5195-3p, and miR-663b is hsa-miR-663b. miR-6765-5p is hsa-miR-6765-5p, miR-4513 is hsa-miR-4513, miR-614 is hsa-miR-614, miR-6785-5p is hsa-miR-6785-5p, miR-6777-5p is hsa-miR-6777-5p, miR-940 is hsa-miR-940, miR-4741 is hsa-miR-4741, miR-6870-5p is hsa-miR-6870-5p, and miR-6131 is hsa-miR-6131;miR-150-3p is hsa-miR-150-3p, miR-4707-5p is hsa-miR-4707-5p, miR-1915-3p is hsa-miR-1915-3p, miR-3937 is hsa-miR-3937, miR-937-5p is hsa-miR-937-5p, miR-4443 is hsa-miR-4443, miR-1914-3p is hsa-miR-1914-3p, miR-3620-5p is hsa-miR-3620-5p, and miR-1268b is hsa-miR- 1268b, miR-1227-5p is hsa-miR-1227-5p, miR-6880-5p is hsa-miR-6880-5p, miR-4417 is hsa-miR-4417, miR-6802-5p is hsa-miR-6802-5p, miR-6769a-5p is hsa-miR-6769a-5p, miR-663a is hsa-miR-663a, miR-6721-5p is hsa-miR-6721-5p, miR-4532 is hsa-miR-4532, and miR-7977 is hsa-miR-7977, miR-92b-5p, hsa-miR-92b-5p, miR-371a-5p, hsa-miR-371a-5p, miR-6126, hsa-miR-6126, miR-4734, hsa-miR-4734, miR-4665-3p, hsa-miR-4665-3p, miR-423-5p, hsa-miR-423-5p, miR-1469, hsa-miR-1469, miR-4675, hsa-miR-4675, and miR-1915-5p. a-miR-1915-5p, miR-6716-5p is hsa-miR-6716-5p, miR-718 is hsa-miR-718, miR-4281 is hsa-miR-4281, miR-6820-5p is hsa-miR-6820-5p, miR-6795-5p is hsa-miR-6795-5p, miR-6779-5p is hsa-miR-6779-5p, miR-7109-5p is hsa-miR-7109-5p, miR-6798-5p is hsa-miR-6798-5p,miR-4648 is hsa-miR-4648, miR-8059 is hsa-miR-8059, miR-6765-3p is hsa-miR-6765-3p, miR-6132 is hsa-miR-6132, miR-4492 is hsa-miR-4492, miR-7107-5p is hsa-miR-7107-5p, miR-3195 is hsa-miR-3195, miR-3180 is hsa-miR-3180, miR-296-3p is hsa-miR-296-3p, and miR-56 4 is hsa-miR-564, miR-1268a is hsa-miR-1268a, miR-6848-5p is hsa-miR-6848-5p, miR-762 is hsa-miR-762, miR-2861 is hsa-miR-2861, miR-1203 is hsa-miR-1203, miR-1260b is hsa-miR-1260b, miR-4476 is hsa-miR-4476, miR-6885-5p is hsa-miR-6885-5p, and miR-6769b-5p is hsa- miR-6769b-5p, miR-23b-3p is hsa-miR-23b-3p, miR-1343-5p is hsa-miR-1343-5p, miR-3621 is hsa-miR-3621, miR-4688 is hsa-miR-4688, miR-4286 is hsa-miR-4286, miR-4640-5p is hsa-miR-4640-5p, miR-4739 is hsa-miR-4739, miR-1260a is hsa-miR-1260a, and miR-4276 is hsa- miR-4276, and miR-7106-5p is hsa-miR-7106-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6774-5p is hsa-miR-6774-5p, miR-4707-3p is hsa-miR-4707-3p, miR-4534 is hsa-miR-4534, miR-4294 is hsa-miR-4294, miR-6850-5p is hsa-miR-6850-5p, miR-6089 is hsa-miR-6089, andmiR-671-5p is hsa-miR-671-5p.
[0581] In a preferred embodiment of the method of the present invention, the nucleic acid (specifically, the probe or primer) is a polynucleotide shown in the following (a) to (e): (a) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a nucleotide sequence in which u is t in the nucleotide sequence, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides; (b) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642; (c) a polynucleotide consisting of a base sequence complementary to any of the base sequences represented by SEQ ID NOs: 1 to 165 and 635 to 642, or the base sequence in which u is t, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 1 to 165 and 635 to 642, or a base sequence in which u is t in the base sequence; and (e) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d); is selected from the group consisting of:
[0582] The methods of the present invention can also use nucleic acids capable of specifically binding to at least one polynucleotide selected from miR-128-2-5p, miR-125a-3p, miR-92a-2-5p, and miR-486-3p.
[0583] In a preferred embodiment, such nucleic acids are specifically: miR-128-2-5p is hsa-miR-128-2-5p; miR-125a-3p is hsa-miR-125a-3p; miR-92a-2-5p is hsa-miR-92a-2-5p; and miR-486-3p is hsa-miR-486-3p.
[0584] Furthermore, in a preferred embodiment, specifically, such nucleic acids are polynucleotides shown in (f) to (j) below: (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 166 to 169, or a base sequence in which u is t in the base sequence, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 166 to 169; (h) a polynucleotide comprising a nucleotide sequence complementary to any one of SEQ ID NOs: 166 to 169, or a nucleotide sequence in which u is t in the nucleotide sequence, or a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides; (i) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 166 to 169, or a base sequence in which u is t in the base sequence; and (j) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i); is selected from the group consisting of:
[0585] The methods of the present invention further include miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5p, miR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-3656, miR-6782-5p A nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141, and miR-1199-5p can be used.
[0586] In a preferred embodiment, such nucleic acids are specifically: miR-3196 is hsa-miR-3196; miR-211-3p is hsa-miR-211-3p; miR-4271 is hsa-miR-4271; miR-6851-5p is hsa-miR-6851-5p; miR-149-3p is hsa-miR-149-3p; miR-4667-5p is hsa-miR-4667-5p; and miR-135a-3p is hsa-miR-135a-3p. p, miR-4486 is hsa-miR-4486, miR-4697-5p is hsa-miR-4697-5p, miR-4725-3p is hsa-miR-4725-3p, miR-6510-5p is hsa-miR-6510-5p, miR-5001-5p is hsa-miR-5001-5p, miR-4673 is hsa-miR-4673, miR-4466 is hsa-miR-4466, and miR-23a-3p is hsa-miR -23a-3p, miR-3656 is hsa-miR-3656, miR-6782-5p is hsa-miR-6782-5p, miR-4689 is hsa-miR-4689, miR-451a is hsa-miR-451a, miR-4446-3p is hsa-miR-4446-3p, miR-3180-3p is hsa-miR-3180-3p, miR-642a-3p is hsa-miR-642a-3p, and miR-6889-5p is hsa-miR-6889-5p, miR-3178 is hsa-miR-3178, miR-4665-5p is hsa-miR-4665-5p, miR-6722-3p is hsa-miR-6722-3p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-4507 is hsa-miR-4507, miR-3141 is hsa-miR-3141, and miR-1199-5p is hsa-miR-1199-5p.
[0587] More specifically, the nucleic acid is a polynucleotide shown in (k) to (o) below: (k) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 170 to 199, or a base sequence in which u is t in the base sequence, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 170 to 199; (m) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any one of SEQ ID NOs: 170 to 199, or a nucleotide sequence in which u is t in the nucleotide sequence; a variant thereof; a derivative thereof; or a fragment thereof comprising 15 or more consecutive nucleotides; (n) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 170 to 199, or a base sequence in which u is t in the base sequence; and (o) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (k) to (n); The polynucleotide is selected from the group consisting of:
[0588] Examples of specimens used in the method of the present invention include specimens prepared from a subject's biological tissue (preferably stomach tissue), blood, serum, plasma, urine, and other body fluids. Specifically, specimens for measurement can be prepared from RNA-containing specimens prepared from the tissue, specimens containing polynucleotides further prepared from the tissue, blood, serum, plasma, urine, and other body fluids, and specimens obtained by biopsy or other means from a part or all of a subject's biological tissue, or biological tissue removed by surgery.
[0589] As used herein, a subject refers to a mammal, such as, but not limited to, a human, a monkey, a mouse, a rat, etc., and is preferably a human.
[0590] The steps of the method of the present invention can be changed depending on the type of specimen to be measured.
[0591] When RNA is used as the measurement target, gastric cancer (cells) can be detected, for example, by the following steps (a), (b), and (c): (a) combining RNA prepared from a sample of a subject or a complementary polynucleotide (cDNA) transcribed therefrom with a polynucleotide in a kit or device of the present invention; (b) measuring the sample-derived RNA or cDNA synthesized from the RNA bound to the polynucleotide by hybridization using the polynucleotide as a nucleic acid probe or by quantitative RT-PCR using the polynucleotide as a primer; (c) assessing the presence or absence of gastric cancer (or its associated gene expression) based on the measurement results of (b) above; may include:
[0592] For example, various hybridization methods can be used to detect, test, evaluate, or diagnose gastric cancer (or its resulting gene expression) in vitro using the present invention, including Northern blotting, Southern blotting, RT-PCR, DNA chip analysis, in situ hybridization, Northern hybridization, and Southern hybridization.
[0593] When using the Northern blot method, the presence or absence of expression of each gene in RNA and the expression level thereof can be detected and measured by using the above-mentioned nucleic acid probes that can be used in the present invention. Specifically, the nucleic acid probe (complementary strand) can be ionized with a radioisotope ( 32 P, 33 P, 35 An example of such a method is to label the DNA / RNA with a radioisotope or fluorescent substance, and then hybridize it with RNA derived from the subject's biological tissue that has been transferred to a nylon membrane or the like in a standard manner. Then, the signal derived from the label (radioisotope or fluorescent substance) of the formed DNA / RNA double strand is detected and measured using a radiation detector (e.g., BAS-1800II (Fuji Photo Film Co., Ltd.)) or a fluorescence detector (e.g., STORM 865 (GE Healthcare)).
[0594] When quantitative RT-PCR is used, the presence or absence of gene expression in RNA and its expression level can be detected and measured by using the primers usable in the present invention. Specifically, a method can be exemplified in which cDNA is prepared from RNA derived from a subject's biological tissue in a standard manner, and then a pair of primers (consisting of a forward strand and a reverse strand that bind to the cDNA) of the present invention is hybridized to the cDNA to amplify the target gene region using the cDNA as a template, followed by PCR in a standard manner to detect the resulting double-stranded DNA. Methods for detecting double-stranded DNA include PCR using primers pre-labeled with a radioisotope or fluorescent substance, electrophoresis of PCR products on agarose gel, and staining and detecting double-stranded DNA with ethidium bromide or the like, and transferring the resulting double-stranded DNA to a nylon membrane or the like in a standard manner, followed by hybridization with a labeled nucleic acid probe for detection.
[0595] When nucleic acid array analysis is used, an RNA chip or DNA chip is used in which the nucleic acid probe (single-stranded or double-stranded) of the present invention is attached to a substrate (solid phase). The area where the nucleic acid probe is attached is called a probe spot, and the area where the nucleic acid probe is not attached is called a blank spot. A group of genes immobilized on a substrate is generally called a nucleic acid chip, nucleic acid array, microarray, etc., and DNA or RNA arrays include DNA or RNA macroarrays and DNA or RNA microarrays, but in this specification, the term "chip" is intended to include such arrays. The DNA chip may be, but is not limited to, the 3D-Gene (registered trademark) Human miRNA Oligo chip (Toray Industries, Inc.).
[0596] Measurement of DNA chips is not limited to, but an example of a method is to detect and measure signals derived from labeled nucleic acid probes using an image detector (e.g., Typhoon 9410 (GE Healthcare) or 3D-Gene (registered trademark) Scanner (Toray Industries, Inc.)).
[0597] As used herein, "stringent conditions" refer to conditions under which a nucleic acid probe hybridizes to its target sequence to a greater extent than to other sequences (e.g., a measurement value of at least the mean of the background measurement value plus twice the standard error of the background measurement value), as described above.
[0598] Stringent conditions are defined by the conditions for hybridization and subsequent washing. Hybridization conditions are not limited, but include, for example, 30°C to 60°C, for 1 to 24 hours in a solution containing SSC, a surfactant, formamide, dextran sulfate, a blocking agent, and the like. Here, 1x SSC is an aqueous solution (pH 7.0) containing 150 mM sodium chloride and 15 mM sodium citrate, and surfactants include SDS (sodium dodecyl sulfate), Triton, Tween, and the like. Hybridization conditions more preferably include 3 to 10x SSC and 0.1 to 1% SDS. Another example of stringent conditions is post-hybridization washing conditions, such as sequential washing with a solution containing 0.5xSSC and 0.1% SDS at 30°C, a solution containing 0.2xSSC and 0.1% SDS at 30°C, and a 0.05xSSC solution at 30°C. It is desirable that the complementary strand maintains a hybridized state with the target positive strand even when washed under such conditions. Specific examples of such complementary strands include a strand consisting of a nucleotide sequence that is completely complementary to the nucleotide sequence of the target positive strand, and a strand consisting of a nucleotide sequence that shares at least 80%, preferably at least 85%, more preferably at least 90% or at least 95%, e.g., at least 98% or at least 99%, identity with the target strand.
[0599] Other examples of "stringent conditions" for these hybridizations are described, for example, in Sambrook, J. & Russell, D., Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, published January 15, 2001, Vol. 1, 7.42-7.45, Vol. 2, 8.9-8.17, and can be used in the present invention.
[0600] Examples of conditions for performing PCR using the polynucleotide fragments in the kit of the present invention as primers include using a PCR buffer with a composition such as 10 mM Tris-HCl (pH 8.3), 50 mM KCL, and 1 to 2 mM MgCl2, and treating for approximately 15 seconds to 1 minute at a temperature that is 5 to 10°C above the Tm value calculated from the primer sequence. Methods for calculating the Tm value include Tm value = 2 × (number of adenine residues + number of thymine residues) + 4 × (number of guanine residues + number of cytosine ...
Claims
1. A kit for detecting stomach cancer, comprising a nucleic acid capable of specifically binding to a polynucleotide of miR-8063, a stomach cancer marker.
2. The kit of claim 1, wherein the nucleic acid is selected from the group consisting of the polynucleotides (a) to (d) below: (a) a polynucleotide consisting of the base sequence represented by SEQ ID NO: 8 or the base sequence in which u is t; (b) a polynucleotide containing the base sequence represented by SEQ ID NO: 8 or the base sequence in which u is t; (c) a polynucleotide consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 8 or the base sequence in which u is t; and (d) A polynucleotide comprising a base sequence complementary to the base sequence represented by SEQ ID NO: 8 or the base sequence in which u is t.
3. The kit includes other gastric cancer markers, namely miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p,The group consisting of miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089, miR-671-5p, miR-128-2-5p, miR-125a-3p, miR-92a-2-5p and miR-486-3p, and / or miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5pmiR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-365 6, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR-6 The kit according to claim 1 or 2, further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141, and miR-1199-5p.
4. The kit according to claim 3, wherein the nucleic acid is selected from the group consisting of the polynucleotides (e) to (l) below: (e) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 2 to 7, 9 to 71, 73 to 127, 129 to 165, 635 to 642, and 166 to 169, or the base sequence in which u is t; (f) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 2 to 7, 9 to 71, 73 to 127, 129 to 165, 635 to 642, and 166 to 169, or the base sequence in which u is t; (g) a polynucleotide consisting of a base sequence complementary to any one of SEQ ID NOs: 2 to 7, 9 to 71, 73 to 127, 129 to 165, 635 to 642, and 166 to 169, or the base sequence in which u is t; (h) a polynucleotide comprising a base sequence complementary to any of the base sequences represented by SEQ ID NOs: 2 to 7, 9 to 71, 73 to 127, 129 to 165, 635 to 642, and 166 to 169, or the base sequence in which u is t; (I) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 170 to 199 or a base sequence in which u is t in the base sequence; (J) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 170 to 199 or a base sequence in which u is t in the base sequence; (k) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 170 to 199 or the base sequence in which u is t; and (L) A polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 170 to 199 or the base sequence in which u is t.
5. A method for assisting in the detection of gastric cancer, comprising measuring the expression level of a target nucleic acid in a specimen from a subject using the kit according to any one of claims 1 to 4, and evaluating in vitro whether the subject is affected with gastric cancer or not using the measured expression level and a control expression level similarly measured in a healthy subject.
6. A method for assisting in the detection of gastric cancer, comprising measuring the expression level of a target nucleic acid in a specimen from a subject using a device for detecting gastric cancer, the device comprising a nucleic acid capable of specifically binding to a polynucleotide of miR-8063, a gastric cancer marker, and evaluating in vitro whether the subject is affected with gastric cancer or not, using the measured expression level and a control expression level similarly measured in a healthy subject.
7. The method of claim 6, wherein the nucleic acid is selected from the group consisting of the polynucleotides shown in (a) to (d) below: (a) a polynucleotide consisting of the base sequence represented by SEQ ID NO: 8 or the base sequence in which u is t; (b) a polynucleotide containing the base sequence represented by SEQ ID NO: 8 or the base sequence in which u is t; (c) a polynucleotide consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 8 or the base sequence in which u is t; and (d) A polynucleotide comprising a base sequence complementary to the base sequence represented by SEQ ID NO: 8 or the base sequence in which u is t.
8. The device is another gastric cancer marker, miR-6726-5p, miR-1343-3p, miR-1247-3p, miR-6787-5p, miR-6875-5p, miR-1225-3p, miR-6781-5p, miR-4746-3p, miR-1908-5p, miR-6756-5p, miR-204-3p, miR-4651, miR-6757-5p, miR-6825-5p, miR-7108-5p, miR-4792, miR-7641, miR-3188, miR-3131, miR-6780b-5p, miR-8069, miR-6840-3p, miR-8072, miR-1233-5p, miR-6887-5p, miR-1231, miR-5572, miR-6738-5p, miR-6784-5p, miR-6791-5p, miR-6749-5p, miR-6741-5p, miR-128-1-5p, miR-4419b, miR-6746-5p, miR-3184-5p, miR-3679-5p, miR-7110-5p, miR-4516, miR-6717-5p, miR-6826-5p, miR-4433b-3p, miR-3679-3p, miR-3135b, miR-3622a-5p, miR-711, miR-4467, miR-6857-5p, miR-6515-3p, miR-1225-5p, miR-187-5p, miR-3185, miR-642b-3p, miR-1249, miR-744-5p, miR-4442, miR-1228-3p, miR-939-5p, miR-6845-5p, miR-887-3p, miR-7845-5p, miR-6729-5p, miR-4632-5p, miR-615-5p, miR-6724-5p, miR-4728-5p, miR-6732-5p, miR-6816-5p, miR-4695-5p, miR-7975, miR-3197, miR-6125, miR-4433-3p, miR-6727-5p, miR-4706, miR-7847-3p, miR-6805-3p, miR-6766-3p, miR-1913, miR-4649-5p, miR-602, miR-3663-3p, miR-6893-5p, miR-6861-5p, miR-4449, miR-6842-5p, miR-4454, miR-5195-3p,The group consisting of miR-663b, miR-6765-5p, miR-4513, miR-614, miR-6785-5p, miR-6777-5p, miR-940, miR-4741, miR-6870-5p, miR-6131, miR-150-3p, miR-4707-5p, miR-1915-3p, miR-3937, miR-937-5p, miR-4443, miR-1914-3p, miR-3620-5p, miR-1268b, miR-1227-5p, miR-6880-5p, miR-4417, miR-6802-5p, miR-6769a-5p, miR-663a, miR-6721-5p, miR-4532, miR-7977, miR-92b-5p, miR-371a-5p, miR-6126, miR-4734, miR-4665-3p, miR-423-5p, miR-1469, miR-4675, miR-6716-5p, miR-718, miR-4281, miR-6820-5p, miR-6795-5p, miR-6779-5p, miR-7109-5p, miR-6798-5p, miR-4648, miR-8059, miR-6765-3p, miR-6132, miR-4492, miR-7107-5p, miR-3195, miR-3180, miR-296-3p, miR-564, miR-1268a, miR-6848-5p, miR-762, miR-2861, miR-1203, miR-1260b, miR-4476, miR-6885-5p, miR-6769b-5p, miR-23b-3p, miR-1343-5p, miR-3621, miR-4688, miR-4286, miR-4640-5p, miR-4739, miR-1260a, miR-4276, miR-7106-5p, miR-6794-5p, miR-6774-5p, miR-4707-3p, miR-4534, miR-4294, miR-6850-5p, miR-6089, miR-671-5p, miR-128-2-5p, miR-125a-3p, miR-92a-2-5p and miR-486-3p, and / or miR-3196, miR-211-3p, miR-4271, miR-6851-5p, miR-149-3p, miR-4667-5p, miR-135a-3p, miR-4486, miR-4697-5pmiR-4725-3p, miR-6510-5p, miR-5001-5p, miR-4673, miR-4466, miR-23a-3p, miR-365 6, miR-6782-5p, miR-4689, miR-451a, miR-4446-3p, miR-3180-3p, miR-642a-3p, miR- The method according to claim 6 or 7, further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-6889-5p, miR-3178, miR-4665-5p, miR-6722-3p, miR-30c-1-3p, miR-4507, miR-3141, and miR-1199-5p.
9. The method of claim 8, wherein the nucleic acid is selected from the group consisting of the polynucleotides shown in (e) to (l) below: (e) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 2 to 7, 9 to 71, 73 to 127, 129 to 165, 635 to 642, and 166 to 169, or the base sequence in which u is t; (f) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 2 to 7, 9 to 71, 73 to 127, 129 to 165, 635 to 642, and 166 to 169, or the base sequence in which u is t; (g) a polynucleotide consisting of a base sequence complementary to any one of SEQ ID NOs: 2 to 7, 9 to 71, 73 to 127, 129 to 165, 635 to 642, and 166 to 169, or the base sequence in which u is t; (h) a polynucleotide comprising a base sequence complementary to any of the base sequences represented by SEQ ID NOs: 2 to 7, 9 to 71, 73 to 127, 129 to 165, 635 to 642, and 166 to 169, or the base sequence in which u is t; (I) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 170 to 199 or a base sequence in which u is t in the base sequence; (J) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 170 to 199 or a base sequence in which u is t in the base sequence; (k) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 170 to 199 or the base sequence in which u is t; and (L) A polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 170 to 199 or the base sequence in which u is t.
10. The method according to any one of claims 6 to 9, wherein the device is a device for measurement by hybridization technology.
11. The method of claim 10, wherein the hybridization technique is a nucleic acid array technique.
12. The method of any one of claims 5 to 11, wherein the subject is a human.
13. The method according to any one of claims 5 to 12, wherein the sample is blood, serum, or plasma.
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