Identification and analysis of circulating miRNAs in Ovarian clear cell carcinoma

Research Project

Project/Area Number	15K10733
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Obstetrics and gynecology
Research Institution	Tokyo Medical University
Principal Investigator	NISHI HIROTAKA 東京医科大学, 医学部, 主任教授 (60307345)
Co-Investigator(Kenkyū-buntansha)	岡本愛光東京慈恵会医科大学, 医学部, 教授 (20204026)
Project Period (FY)	2015-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	miRNA / 卵巣癌 / 明細胞癌 / 腫瘍マーカー / 明細胞線癌
Outline of Final Research Achievements	We analyzed circulating serum miRNAs in patients with ovarian clear cell carcinoma using the microRNA array. We found that the expression of several miRNAs was significantly different in ovarian clear cell carcinoma samples compared with control samples. Among these miRNAs, the expression level of miR-146a and miR-191 were significantly different in the serum samples from ovarian clear cell carcinoma patients, compared with healthy controls using realtime RT-PCR. Also, we found that miR-146a targeted ARID1A which is related to cremation remodeling. Overexpression of miR-146a significantly decreased the ARID1A expression in ovarian clear cell carcinoma cell lines. Our results provide evidence that regulation of the ARID1A expression by miR-146a may represent a mechanism for ovarian clear cell carcinogenesis.
Academic Significance and Societal Importance of the Research Achievements	今回の成果から血清中miR-146aおよびmiR-191の発現は、感度・特異度に優れた卵巣明細胞癌のバイオマーカーとなる可能性が高く、診断キットなどへの応用が比較的容易に行えるものと思われる。アッセイも末梢血の採血のみであるため、患者に対する侵襲度も低い。そのため、本研究で得られる成果をもとに、企業等との共同開発による診断方法の確立を考えている。また、miR-146aとその標的遺伝子ARID1Aの相関性の機能解析により、プレシジョン医療等新規治療法の開発の端緒となる可能性がある。