Identification of microRNA underying the common pathogenic mechanism of lung cancer and interstitial pneumonia and establishment of a basis for its therapeutic application

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09671
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tokyo Medical University
• Principal Investigator: Nobuyuki Koyama 東京医科大学, 医学部, 教授 (30353460)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 非小細胞肺癌 / 間質性肺炎 / マイクロRNA / 上皮間葉転換 / 筋線維芽細胞分化 / 転移 / 浸潤 / 肺線維化

Outline of Final Research Achievements

Both lung cancer and interstitial pneumonia are refractory and highly comorbid diseases. In the present study, we identified miR-X of microRNA (miRNA) that commonly suppressed the mechanism underlying the development and progression of both diseases.
Using comprehensive miRNA expression analysis, we found commonly decreased expression levels of miR-X in lung cancer and interstitial pneumonia tissues in patients with comorbid lung cancer and interstitial pneumonia, compared to those in healthy lung and lung cancer tissues in patients with lung cancer without interstitial pneumonia.　Overexpression of miR-X suppressed cell growth and epithelial-mesenchymal transition involved in cancer metastasis and invasion in lung cancer cell lines and inhibited differentiation of fibroblasts to myofibroblasts as an indicator of pulmonary fibrogenesis. These findings shown in in vitro assays were confirmed in in vivo assays using disease model mice.

Free Research Field

呼吸器病学

Academic Significance and Societal Importance of the Research Achievements

難治性疾患である肺癌と間質性肺炎は高率に合併し、間質性肺炎合併肺癌は治療選択肢が乏しく、予後不良である。本研究で同定したmiR-Xは、肺癌と間質性肺炎の発症・進展を共通に抑制した。miR-Xの同定と細胞および疾患モデルマウスを用いたmiR-X効果の検証により、肺癌と間質性肺炎の新たな発症・進展機序が明らかになるとともに、両疾患のみならず間質性肺炎合併肺癌に対するmiR-Xを用いた新たな治療の開発、臨床応用への基盤となることが期待できる。さらに、miR-Xは短鎖非コードRNAであるマイクロRNA（miRNA）であり、肺癌、間質性肺炎に対するこれまでにはない治療モダリティーの開発が期待される。