Elucidation of ISG-mediated suppression of mesenchymal tumor stromal cells by miRNAs in human T cell-released exosomes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15275
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Mie University
• Principal Investigator: Momose Fumiyasu 三重大学, 医学系研究科, 産学官連携講座助教 (20798326)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: エクソソーム / miRNA / 間葉系幹細胞 / ISG / Type-I IFN

Outline of Final Research Achievements

In the development of inhibitors for modulation of mesenchymal tumor stroma, we have identified that the exosomal miR-6089 and miR-6090 released by human T cells have a possibility to suppress mesenchymal stem cell (MSC) activity in an interferon-stimulated gene (ISG)-mediated manner. In this study, we tried to investigate whether miR-6089 and miR-6090 induce ISGs and type I IFN-related genes, and consequently influence on MSC activities by establishing those miRNA-overexpression cell line models. As a result, miR-6089 and miR-6090 were found to enhance ISGs and type I IFN-related genes, such as IFN-β, expressions and influence on the proliferation and differentiation of MSCs. Our finding suggest that those miRNAs play a critical role in MSC activities in an ISG-mediated manner.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

転移を伴うがん患者の生存率は、早期がん患者と比べ著しく低下する。そのため、現在がんの浸潤・転移を標的とした治療薬の早急な開発が社会的に求められている。本研究では、T細胞エクソソームに含まれるmiRNAsがISGsやIFN関連遺伝子を誘導し、がんの浸潤・転移を促進するMSCを抑制することを見出した。この様ながん間質細胞にフォーカスしたExosomal miRNAsの作用は世界的にも稀少で、がん転移機構の解明にとって重要である。本研究成果を踏まえた今後の発展により本機構が解明できれば、従来の抗がん剤とは異なる新規機序のがん浸潤・転移阻害薬を創製し、がん創薬研究が大きく進展する可能性が期待される。