Analyis of RNA helicase A function on Ewing's sarcoma-specific fusion gene

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09576
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Oita University
• Principal Investigator: Itonaga Ichiro 大分大学, 医学部, 講師 (10295181)
• Co-Investigator(Kenkyū-buntansha): 河野 正典 大分大学, 医学部, 助教 (30571773)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Ewing肉腫

Outline of Final Research Achievements

The causative gene for Ewing's sarcoma is EWS-Fli1, which is a fusion of EWS involved in RNA metabolism and the transcription factor Fli1. Carcinogenesis caused by EWS-Fli1 has been thought to be due to abnormalities in transcription factor function on the Fli1 side. However, in recent years, it has been reported that RNA helicase A (RHA) binds to EWS-Fli1 and that the small molecule compound YK-4-279, which inhibits the binding, suppresses the growth of Ewing sarcoma cells. The purpose of this study is to elucidate the details of the interaction between EWS-Fli1 and RHA, and to clarify the carcinogenic mechanism of Ewing sarcoma due to abnormal RNA metabolism.

Free Research Field

肉腫

Academic Significance and Societal Importance of the Research Achievements

近年の海外の研究により、EWS-Fli1がRHAに結合しRHAの機能を阻害すること、YK-4-279がその結合を阻害することが報告された。しかし、YK-4-279によりどのような遺伝子の発現が変化するか、またYK-4-279は融合遺伝子のどの部分に作用しているか、などの詳細については未だ不明である。YK-4-279を用いて、EWS-Fli1とRHAとの結合部位や、RHA機能阻害のメカニズムの詳細、アポトーシス誘導の分子機構が解明できる可能性がある。さらに、融合遺伝子にEWSを有する疾患群に対しての治療標的の発見に繋がる可能性もあり、本研究の意義は大きい。