Classification of extracellular miRNAs by function and routes of their secretion

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19489
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: National Cancer Center Japan
• Principal Investigator: Tsuchiya Naoto 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (30322712)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: 細胞外miRNA

Outline of Final Research Achievements

Extracellular vesicles are regulators of miRNA-mediated intercellular communications to maintain malignant properties of cancer cells. However, detailed mechanisms of how specific miRNAs selected and secreted from cancer cells are not fully understood. We aimed to understand the mechanism of miRNA secretion and to classify extracellular miRNAs by their functions. We found secretion of a similar subset of miRNAs from sarcoma cells. Two of them were found to induce the differentiation of monocyte to macrophage. Protein X was suggested to be secreted as vesicles (or complexes), which are distinct from exosomes. The RNA processing proteins and specific miRNAs were enriched in the protein X fraction. Secretion of these miRNAs were not affected by an exosome inhibitor. Screening intracellular molecules indicated the binding of the protein X with Exportins and RAB family proteins. These results suggest that the protein X is regulator for the intracellular protein and miRNA trafficking.

Free Research Field

分子細胞性bつ学

Academic Significance and Societal Importance of the Research Achievements

細胞外へと分泌されるmiRNAの機能が様々なヒト疾患の病態誘発に重要な役割を有することは疑いない事実であるが、分泌機能の詳細とそれらの機能、特に腫瘍微小環境中に存在する非腫瘍細胞への影響は不明な点が多い。本研究の成果は、疾患誘発の分子機構について、ゲノム解析等では理解困難な問題を解き明かすことに有用となり、新たな作用機序に基づく治療・診断法の開発に向けた科学的根拠を提示する。