2021 Fiscal Year Final Research Report

Search for synthetic lethal candidates for PIK3CA mutations

Research Project

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Project/Area Number	19K09809
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	Mika Nagayasu 奈良県立医科大学, 医学部, 助教 (80623496)
Co-Investigator(Kenkyū-buntansha)	松原翔奈良県立医科大学, 医学部附属病院, 研究員 (20825236) 小林浩奈良県立医科大学, 医学部, 研究員 (40178330) 小川憲二奈良県立医科大学, 医学部附属病院, 研究員 (60623494) 河原直紀奈良県立医科大学, 医学部, 助教 (70623495) 山中彰一郎奈良県立医科大学, 医学部附属病院, 研究員 (30866009)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	卵巣明細胞癌 / 合成致死 / ARID1A遺伝子変異 / Cyclin-E1 / CCNE1
Outline of Final Research Achievements	Cyclin-E1 (CCNE1) was identified as a candidate for synthetic lethality of the ARID1A mutation; interference with CCNE1 inhibited growth of the ARID1A mutant strain and had no effect on the ARID1A wild strain. Cell cycle analysis suggested inhibition of G1-S transition and induction of apoptosis, which was confirmed by apoptosis assays. Furthermore, in a xenograft mouse model, interference with CCNE1 effectively inhibited tumor cell growth. This study demonstrates for the first time that CCNE1 is a synthetic lethal target gene for ovarian clear cell carcinoma lines with ARID1A mutations. Targeting this gene is expected to be a novel anticancer strategy in the treatment of ovarian clear cell carcinoma.
Free Research Field	癌分子生物学
Academic Significance and Societal Importance of the Research Achievements	本研究により、CCNE1がARID1A変異を有する卵巣明細胞癌株に対する合成致死標的遺伝子であることが初めて示された。この遺伝子を標的とすることは、卵巣明細胞癌治療における新規の抗がん戦略として期待される。