Exploration of new therapeutic target for ovarian cancer applying CRISPR library screening system

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16800
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Yamamoto Akiko 東京医科大学, 医学部, 講師 (50531224)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 卵巣癌 / CRISPR / MYC / 癌遺伝子

Outline of Final Research Achievements

We applied a reporter system to evaluate the transcriptional activity of MYC in ovarian cancer cell OVSAHO, which we had independently developed in our previous research and conducted a comprehensive analysis using the CRISPR activation library (SAM) for unveiling molecules that increase the transcriptional activity of MYC. The system was modified to avoid the binding of MYC itself gRNAs. Based on the next-generation sequencing results, we used existing databases to select 14 candidate molecules that would contribute to the regulation of MYC transcriptional activity. When candidate gRNA molecules were introduced into cells using the CRISPR system and the Dual-Luciferase assay was performed, seven molecules were shown to statistically significantly increase MYC transcriptional activity.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

卵巣癌は予後不良であり新たな治療法の確立が急務である。近年、癌の遺伝子解析とその結果に基づき治療方針を決定するがんゲノム医療の必要性が高まっている。癌遺伝子の一つであるMYCは、卵巣癌では他の癌腫に比し高頻度で増幅していることを鑑みると、卵巣癌の発生や進展、再発に重要な役割を担っていると予測され、新たな治療ターゲットとなり得るだろうと想定される。今回の研究によりMYCの転写活性を調節する分子が同定できたことは、卵巣癌におけるMYC発現制御システムの解明の一助となると予想され、さらにこの結果を応用しMYCをターゲットとした阻害薬の開発が進めば卵巣癌の新たな治療戦略として位置づけられると期待する。