Mechanisms of Src-mediated selective miRNA sorting into exosomes.

• Project/Area Number: 18K07221
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Osaka University (2019-2021); Aichi Cancer Center Research Institute (2018)
• Principal Investigator: NAITO Yoko 大阪大学, 免疫学フロンティア研究センター, 特任研究員(常勤) (10553026)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: エクソソーム / miRNA / がん進展 / 選択的内包化 / 細胞外小胞 / microRNA / Src / がん原遺伝子 / がん微小環境

Outline of Final Research Achievements

Exosomal microRNAs (miRNA) have been reported to be able to regulate multiple biological events and pathological processes. However, it’s not clear how specific miRNAs are selectively sorted into exosome. Therefore, in this study, I investigated the mechanism(s) by which tumor-related miRNAs are internalized into exosomes during Src-mediated cancer progression. I identified candidate factor that could be carrier by binding to miRNAs and examined how Src and candidate carrier coordinately regulate the internalization of tumor-related miRNA into exosomes.

Academic Significance and Societal Importance of the Research Achievements

エクソソーム内包miRNAの疾患依存的プロファイルや受容細胞への機能解析が多い中、本研究は、がん進展に伴うmiRNAのエクソソーム内包化の制御機構の解明に取り組んだ。エクソソームを標的としたがん治療の方法は、がん細胞によるエクソソーム分泌から受容細胞の取り込みの間の阻害に焦点が当てられている。それに対して、本研究成果は、エクソソーム伝播のさらに上流となる形成過程における、がん進展促進的なmiRNAの内包阻害といった新たな治療戦略の開発に貢献し得る。