Elucidation of the miRNA-EZH2 feedback loop regulating endometrial cancer microenvironment

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11123
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Hokkaido University
• Principal Investigator: Konno Yosuke 北海道大学, 医学研究院, 助教 (10572703)
• Co-Investigator(Kenkyū-buntansha): 董 培新 北海道大学, 医学研究院, 助教 (50602504) ; 櫻木 範明 北海道大学, 医学研究院, 名誉教授 (70153963)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: microRNA

Outline of Final Research Achievements

In this study, we aimed to clarify whether the miRNA-EZH2 feedback loop contributes to EZH2 overexpression in endometrial cancer and whether EZH2 induces the expression of IL-6/8 through miRNAs-mediated signaling pathways. We found that EZH2 and tumor suppressor miRNAs mutually form a negative feedback loop, resulting in enhanced expression of EZH2 and decreased expression of tumor suppressor miRNAs and that EZH2 induces the overproduction of IL-6/8 via miRNAs-mediated pathways in endometrial cancer cells. These findings suggest that targeting and inhibition of EZH2 represents a potential therapeutic strategy for endometrial cancer.

Free Research Field

子宮体癌

Academic Significance and Societal Importance of the Research Achievements

EZH2と癌抑制miRNA群が相互に負のフィードバックループを形成して、EZH2の発現亢進及びlet-7bなどのmiRNAの発現低下を招き、下流にあるTwist、Snail、STAT3経路、NF-κB経路及びWnt/β-catenin経路の活発化を介して、IL-6/8過剰産生及び体癌の悪性化を導くという重要な成果が得られている。本研究により得られた知見は、今後体癌の根絶を目指す基層研究の発展及び新しい治療法の開発に大きく貢献していると考えられる。