Identification and functional analysis of novel biomarker miRNA in cisplatin-induced muscle atrophy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06706
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Hoshi University
• Principal Investigator: Sakai Hiroyasu 星薬科大学, 薬学部, 准教授 (00328923)
• Co-Investigator(Kenkyū-buntansha): 山田 岳史 日本医科大学, 医学部, 准教授 (50307948)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: シスプラチン / 副作用 / 筋萎縮

Outline of Final Research Achievements

Comprehensive analysis revealed that mir-5129-5p was upregulated in both skeletal muscle and plasma in cisplatin-induced muscle atrophy of mice. However, this miRNA was not expressed in humans. Therefore, due to the species difference, applied research using serum samples of patients was not possible. On the other hand, it was clarified that the expression of the mir-29-3p family targeting IGF-1 and the expression of IGF-1 decreased in skeletal muscle in mouse of cisplatin-induced muscle atrophy, and the protein synthesis pathway was suppressed. Furthermore, it was suggested that cisplatin-induced muscle atrophy is suppressed by supplementing with IGF-1. This study suggested that the increased expression of the mir-29-3p family in skeletal muscle could be a diagnostic marker for cisplatin-induced muscle atrophy.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

がん患者において進行性の骨格筋萎縮は予後予測因子となる。がん闘病中患者のこの骨格筋萎縮に対し、「簡便な診断マーカーにて、筋萎縮をより早く診断できるか」、「どう筋量を維持するか」が、臨床上の重要な課題である。そこで本申請では、シスプラチンの筋萎縮発症におけるバイオ（診断）マーカーを新たな視点である miRNA にて探索し、さらには筋萎縮の発症機序の解明を試みた結果、骨格筋中のmir-29-3pファミリーの発現増加はシスプラチンによる筋萎縮時の診断マーカーになり得ることが示唆できた。