Comprehensive analysis and novel epigenomic drug discovery using ChIP sequence in ovarian clear cell adenocarcinoma.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11268
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: SONE KENBUN 東京大学, 医学部附属病院, 助教 (90598872)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ヒストンメチル化酵素 / 卵巣癌 / ChIP-seq / 実験ロボット

Outline of Final Research Achievements

Among ovarian cancers, ovarian clear cell carcinoma (OCCC) is prevalent in Japan, and is chemo-resistant. In this study, we investigated whether histone methyltransferases could be a therapeutic target for OCCC. Overexpression of two histone methyltransferases (WHSC1, SMYD2) was observed in OCCC tissues compared with normal ovarian tissues. Knockdown of WHSC1 and SMYD2 suppressed cell proliferation. A histone methyltransferase EZH2 was also found to regulate WHSC1, and knockdown of SMYD2 induced apoptosis in OCCC cell lines. This suggests that WHSC1 and SMYD2 could be therapeutic targets for ovarian clear cell carcinoma. Next, the protocol development of the next generation ChIP-seq method using the robotics technology for the clinical specimen was carried out. The large-scale research using OCCC clinical sample will be carried out in future.

Free Research Field

婦人科悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

ヒストンメチル化は癌治療のトピックにも関わらず、婦人科癌においては研究が進んでいない状況である。よってOCCCに対するヒストンメチル化酵素を標的とした新規エピゲノム創薬につなげる研究を行う事が目的であり、本研究において上記が達成されたと考える。また今までChIP-seq法は細胞株における解析が主な適応であったが、本研究で臨床検体を使用した次世代型ChIP-seq法を開発した。この解析法は本研究独自のものであり、今後この分野でリードできると考える。