Comprehensive exploration of microRNA expression in renal cell carcinomas by microarray analysis with omics data

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08724
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Gotoh Masahiro 国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (00291138)
• Co-Investigator(Kenkyū-buntansha): 新井 恵吏 慶應義塾大学, 医学部(信濃町), 講師 (40446547)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: マイクロRNA / 腎細胞がん / miR-200 / EMT

Outline of Final Research Achievements

Microarray analysis revealed that 191 miRNAs showed significantly elevated or reduced expression in tumorous tissues of 95 renal cell carcinoma (RCC) cases. Expression alterations of 191 such miRNAs were significantly accumulated in four pathways, which included epithelial-mesenchymal transition (EMT) by MetaCore pathway analysis. Expression levels of 5 EMT-related miRNAs, known as the miR-200 family, were frequently reduced in tumorous tissues. Transfection assay of RCC cell lines also demonstrated that expression levels of the miR-200 family were related to regulation of EMT. Reduced expression of the miR-200 family and/or their target CDH1 mRNA in tumorous tissues was significantly correlated with clinicopathological parameters reflecting tumor aggressiveness, and inversely correlated with the survival rates of patients with RCCs. These data suggest that reduced expression of the miR-200 family may participate in the malignant progression of RCCs resulting in poorer patient outcome.

Free Research Field

がんの分子病理学

Academic Significance and Societal Importance of the Research Achievements

本研究は多数の腎細胞がん症例より得られた質の高いがんおよび対照非がん腎組織検体を用いてmiRNA発現の網羅的解析を行い、腎細胞がんの臨床病理学的悪性度と症例の予後を規定するmiRNAを同定し、腎発がんにおけるmiRNA発現異常の意義を明らかにした。今後、本研究成果を新規治療標的候補やコンパニオン診断マーカーに応用し、腎細胞がんの個別化医療を目指しており、十分に学術的・社会的意義があるものと考える。