MiR-17 and miR-19 cooperatively promote skeletal muscle cell differentiation

Cell Mol Life Sci. 2019 Dec;76(24):5041-5054. doi: 10.1007/s00018-019-03165-7. Epub 2019 Jun 18.

Abstract

Skeletal myogenesis is a highly coordinated process that involves cell proliferation, differentiation and fusion controlled by a complex gene regulatory network. The microRNA gene cluster miR-17-92 has been shown to be related to this process; however, the exact role of each cluster member remains unclear. Here, we show that miR-17 and miR-20a could effectively promote the differentiation of both C2C12 myoblasts and primary bovine satellite cells. In contrast, miR-18a might play a negative role in C2C12 cell differentiation, while miR-19 and miR-92a had little influence. Transcriptome and target analyses revealed that miR-17 could act on Ccnd2, Jak1 and Rhoc genes that are critical for cell proliferation and/or fusion. Notably, the addition of miR-19 could reverse the lethal effect of miR-17 and could thus facilitate the maturation of myotubes. Furthermore, by co-injecting the lentiviral shRNAs of miR-17 and miR-19 into mouse tibialis anterior muscles, we demonstrated the wound healing abilities of the two miRNAs. Our findings indicate that in combination with miR-19, miR-17 is a potent inducer of skeletal muscle differentiation.

Keywords: Muscle regeneration; Myogenic differentiation; Skeletal myogenesis; miR-17–92; microRNA.

MeSH terms

  • Animals
  • Cattle
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics
  • Cyclin D2 / genetics
  • Gene Regulatory Networks / genetics
  • Janus Kinase 1 / genetics
  • Mice
  • MicroRNAs / genetics*
  • Muscle Development / genetics
  • Muscle, Skeletal / growth & development*
  • Muscle, Skeletal / metabolism
  • Myoblasts / metabolism
  • rhoC GTP-Binding Protein / genetics

Substances

  • Ccnd2 protein, mouse
  • Cyclin D2
  • MIRN19 microRNA, mouse
  • MicroRNAs
  • Mirn17 microRNA, mouse
  • Jak1 protein, mouse
  • Janus Kinase 1
  • rhoC GTP-Binding Protein