The identification of circular RNA which is specifically elevated in ovarian cancer and the elucidation of its role

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20967
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Osaka University
• Principal Investigator: Okamura Ayako 大阪大学, 大学院医学系研究科, 技術補佐員 (40910253)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 卵巣がん / 環状RNA / 新規バイオマーカー / 浸潤 / 卵巣癌 / バイオマーカー

Outline of Final Research Achievements

Clear cell carcinoma (CCC) of ovary, at least partly, arises from endometriotic cyst. Underlying mechanisms during this malignant transformation needs to be elucidated. Herein, we focused on circular RNAs (circRNAs) during this process and assessed their roles. Through circRNA microarray using extracted RNAs from two CCCs with each corresponding normal ovarian tissue, circRNAs highly expressed in CCCs were identified. Among 3 candidate circRNAs, circSOD2 were specifically elevated in CCC clinical samples. The interaction between circSOD2 and miR-224-5p as well as miR-532-3p was suggested by in silico analyses, and thereafter verified by RNA pull-down assay. Silencing circSOD2 inhibited cancer invasion in Matrigel Invasion Assay.
As a conclusion, we presented that cirsSOD2 is highly expressed in CCC and showed circSOD2/miR-224-5p/miR-522-3p axis during ovarian cancer invasion. Silencing circSOD2 alleviated cancer cell invasion, suggesting it can be a novel molecular target to treat CCC.

Free Research Field

卵巣がん　婦人科腫瘍　産婦人科

Academic Significance and Societal Importance of the Research Achievements

本研究では卵巣癌に特異的に発現する環状RNAの同定とその機能の解析を行った。具体的には卵巣癌の中でも抗がん剤に対する抵抗性が高く、予後不良である卵巣明細胞癌に焦点を当てた検討を行った。明細胞癌は難治性であり、新規治療の開発が望まれる。本研究により、卵巣明細胞癌において特異的に発現が上昇している環状RNAであるcircSOD2を同定し、そのがん浸潤における役割の一部を解明し、新規分子標的治療の可能性を提示した。