Epigenetic network between histon modification and miRNA in ovarian clear cell carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09775
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tsuruga Tetsushi 東京大学, 医学部附属病院, 講師 (70570448)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ヒストン修飾 / エピゲノムj / 卵巣類内膜癌 / 子宮体癌

Outline of Final Research Achievements

① Therapeutic target of histone methylase EHMT2 in ovarian endometrioid carcinoma was investigated. Increased expression of EMHT2 was observed in ovarian endometrioid carcinoma, and addition of siRNA for EHMT2 and EHMT2 inhibitors to ovarian endometrioid carcinoma suppressed cell proliferation with increasing inflammatory markers and inducing apoptosis. (2) Examination of histone methyl-transferases PRMT6 in endometrial cancer: The mRNA expression level of PRMT6 was high in endometrial cancer, showing a negative correlation with prognosis (p < 0.01). ChIP-seq analysis showed PRMT6 regulate multiple cancer-related transcription factors and interferon factors through histone modification. And, there was the relation of histone H3R2 methylation and histone H3K 27 acetylation.

Free Research Field

エピゲノム

Academic Significance and Societal Importance of the Research Achievements

今までフォーカスされていなかった卵巣類内膜癌に治療標的の可能性、そのメカニズムについて同定した。また子宮体癌に対するPRMT6の治療標的の可能性も追求し、エピゲノムを用いた網羅的解析により様々な新規遺伝子を同定する事ができた。また子宮体癌におけるヒストン修飾間のエピゲノムネットワークも明らかにされ、今後の子宮体癌の治療標的同定に貢献する研究と考える。