Search for synthetic lethal candidates for HNF1beta-USP28-CLASPIN-Chk1 inhibition

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09604
• 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: Nara Medical University
• Principal Investigator: KIMURA Mai 奈良県立医科大学, 医学部, 助教 (30812333)
• Co-Investigator(Kenkyū-buntansha): 吉元 千陽 奈良県立医科大学, 医学部, 研究員 (00526725) ; 小林 浩 奈良県立医科大学, 医学部, 研究員 (40178330) ; 川口 龍二 奈良県立医科大学, 医学部, 准教授 (50382289) ; 河原 直紀 奈良県立医科大学, 医学部, 助教 (70623495)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: HNF-1beta / 卵巣明細胞癌 / GSK-3beta

Outline of Final Research Achievements

Ovarian clear cell carcinoma is characterized by overexpression of HNF-1beta (hepatocyte nuclear factor-1beta).To evaluate in detail the effects of HNF-1beta overexpression on cellular metabolism, we performed an inhibitor screening. As a result, we identified an inhibitor X that acts specifically on cell lines with high HNF-1beta expression. Addition of inhibitor X under the interference of HNF-1beta markedly reduced cell proliferation. We have previously reported that GSK-3beta is located downstream of HNF-1beta, and when GSK-3beta was interfered with TOV-21G and then treated with inhibitor X, a similar inhibition of cell proliferation was observed.

Free Research Field

癌分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、阻害薬X投与が、現在難治性とされている卵巣明細胞癌に対する有効な治療の可能性があると示された。