Functional analysis of microRNA/let-7 in skeletal muscle atrophy and glucose metabolism

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17966
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Okada Hiroshi 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30806831)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: サルコペニア / micro RNA / let-7e

Outline of Final Research Achievements

This study aimed to understand the role of microRNAs (let-7e-5p) in muscle atrophy.The effect of let-7e-5p overexpression or knockdown on the expression of myosin heavy chain, glucose uptake, and mitochondrial function was investigated in C2C12 myotube cells. Moreover, we examined serum let-7e-5p levels among male subjects with type 2 diabetes.
Suppression of let-7e-5p significantly upregulated the expression of myosin heavy chain, glucose uptake, and mitochondrial function. Real-time PCR revealed a possible regulation involving let-7e-5p and Igf2bp2 mRNA and protein in C2C12 cells. The serum let-7e-5p levels were significantly lower, which might be in compensation, in subjects with decreased muscle mass compared to subjects without decreased muscle mass. Let-7e-5p downregulates the expression of Igf2bp2 in myotube cells and inhibits the growth of the myosin heavy chain.
Based on our study, serum level of let-7e-5p may be used as a potential diagnostic marker for muscle atrophy.

Free Research Field

内分泌・代謝内科学

Academic Significance and Societal Importance of the Research Achievements

フレイル(虚弱状態)は精神・心理的脆弱性、社会的脆弱性に加え身体的脆弱性により要介護状態に至る前段階であり、ADLの低下や死亡のリスクとなる。本邦においてフレイルの対策は喫緊の課題である。本研究ではmicroRNA Let-7を抑制することでIgf2bp2の発現が上昇し、骨格筋萎縮が抑制されるという先行知見を得た。核酸医薬によりフレイルが予防しうる可能性を示し、Let-7がその標的となることを発信、提案できる可能性がある。