MiR-204-5p regulates C2C12 myoblast differentiation by targeting MEF2C and ERRγ

Biomed Pharmacother. 2018 May:101:528-535. doi: 10.1016/j.biopha.2018.02.096. Epub 2018 Mar 22.

Abstract

Myogenic differentiation, which occurs in the process of muscle development, is a highly ordered process. Increasing evidence indicates that microRNAs (miRNAs) are important regulators in myogenic processes. In this study, we found that miR-204-5p expression gradually decreased when myoblasts were induced to differentiate. Our results suggested that miR-204-5p blunted myoblast differentiation, which was accompanied with a decreased proportion of myosin heavy chain (MyHC)-positive cells in myoblasts with augmented expression of miR-204-5p. Furthermore, overexpression of miR-204-5p significantly decreased the MyHC composition of slow-twitch fibers in myoblasts. Luciferase activity assays confirmed that miR-204-5p directly targeted the 3'-untranslated region (3'-UTR) of myocyte enhancer factor 2C (MEF2C) and estrogen-related receptor gamma (ERRγ). Small interfering RNA (siRNA) technology successfully inhibited the expression of MEF2C and ERRγ. Interference with MEF2C or ERRγ inhibited myoblast differentiation and the formation of slow-twitch fibers. Meanwhile, co-transfection of either si-MEF2C or si-ERRγ with miR-204-5p mimics resulted in a more severe attenuation of myogenic differentiation. In summary, this study demonstrates that miR-204-5p inhibits myoblast differentiation by targeting MEF2C and ERRγ. Our findings suggest that miR-204-5p is a potential regulator that could influence myogenesis.

Keywords: ERRγ; MEF2C; Myogenesis; Myosin heavy chain; miR-204-5p.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Cell Differentiation / genetics*
  • Cell Line
  • Cell Line, Tumor
  • HeLa Cells
  • Humans
  • MEF2 Transcription Factors / genetics
  • Mice
  • MicroRNAs / genetics*
  • Muscle Development / genetics
  • Myoblasts / physiology*
  • RNA, Small Interfering / genetics
  • Receptors, Estrogen / genetics*

Substances

  • 3' Untranslated Regions
  • Esrrg protein, mouse
  • MEF2 Transcription Factors
  • MIRN204 microRNA, mouse
  • Mef2c protein, mouse
  • MicroRNAs
  • RNA, Small Interfering
  • Receptors, Estrogen