Identification of exosome secretion-suppressive miRNAs and its target genes.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: National Cancer Center Japan
• Principal Investigator: Yoshioka Yusuke (吉岡祐亮) 国立研究開発法人国立がん研究センター, 研究所, 研究員 (60721503)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: エクソソーム / microRNA / がん / がんの転移

Outline of Final Research Achievements

Exosomes serve as versatile intercellular communication vehicles. Cell-to-cell communication via Exosome cargo contributes to cancer progression in the tumor microenvironment and pre-metastatic niche. Therefore, understanding the critical molecular mechanisms underlying the secretion of exosome in cancer cells is an important issue for developing novel therapeutic strategies. Here, using an original screening system based on ExoScreen assay and a miRNA mimic library containing 2042 miRNAs, exosome secretion-suppressive miRNAs were identified in the breast cancer cell line MDA-MB-231D3H2LN, and the prostate cancer cell line PC-3ML. As a result of the validation, miR-194 was found to inhibit exosome secretion in cancer cells. Moreover, NSF attachment protein gamma (NAPG) which appear to be general components of the intracellular membrane fusion apparatus, was identified as a target gene for miR-194.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた成果は、がん細胞が分泌するエクソソームを介した細胞間コミュニケーションを断つ方法の一つとして、新たながん転移予防薬へと繋がる可能性がある。さらにエクソソームが様々な疾患において、発症、または悪性化に繋がることが報告されてきており、特にアルツハイマー病ではミクログリアがエクソソームを介してタウタンパクを周囲の細胞に伝播し、進行させていることなどが報告されている。そのため、本研究で得られた成果は、がんのみならず、神経疾患や免疫疾患等への応用も視野に入れることができる。