Development of microRNA-based liquid biopsy biomarkers and anticancer treatments in digestive system cancers

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08690
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Komatsu Shuhei 京都府立医科大学, 医学(系)研究科(研究院), 特任講師 (40578978)
• Co-Investigator(Kenkyū-buntansha): 大辻 英吾 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20244600)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: microRNA / リキッドバイオプシー / バイオマーカー / エキソソーム / 遊離核酸 / 核酸治療

Outline of Final Research Achievements

Six candidates (miR-126, 133b, 143, 203, 338-3p, 655) of tumour suppressor miRNAs in ESCC were selected by a systematic review of NCBI database. Of these, miR-655 levels were significantly down-regulated in plasma of ESCC patients compared to healthy volunteers by test- and validation-scale analyses. Low levels of plasma miR-655 were significantly associated with lymphatic invasion, lymph node metastasis and advanced stage. Low level of plasma miR-655 was an independent risk factor of lymphatic progression and a poor prognostic factor. Overexpression of miR-655 in ESCC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. Increased plasma miR-655 levels by the subcutaneous injection significantly inhibited lymph node metastasis in mice. Low levels of miR-655 in plasma relate to lymphatic progression and poor outcomes, and the restoration of the plasma miR-655 levels might inhibit tumour and lymphatic progression in ESCC.

Free Research Field

リキッドバイオプシー、核酸治療

Academic Significance and Societal Importance of the Research Achievements

遺伝子発現調節に関わるmicroRNAが体液中で安定していることに注目し、血中microRNAを指標とした消化器癌の次世代型バイオマーカー探索を行ってきた。今回、食道癌患者血中で枯渇している癌抑制型miR-655に注目し、予後、リンパ節転移予測の新規バイオマーカーとして有用であり、マウス皮下投与により血中miR-655の濃度回復で、腫瘍増殖・リンパ節転移抑制の抗癌核酸治療の可能性を明らかにした。