Identification of a novel miR-206-Notch3 pathway regulating mouse myoblasts proliferation

Gene. 2019 May 5:695:57-64. doi: 10.1016/j.gene.2019.01.045. Epub 2019 Feb 11.

Abstract

MicroRNAs (miRNAs) are endogenous short non-coding RNAs and exert their function by targeting mRNAs of genes. miRNA-206 (miR-206) is exclusively expressed in adult skeletal muscles and plays an important role in myogenesis. However, the regulatory mechanisms of miR-206 in myoblasts proliferation and differentiation are still limited. In this study, we validated that Notch3 is a direct target gene of mouse miR-206 using dual-luciferase reporter assay and miR-206-overexpressed experiments. Furthermore, we demonstrated that the negative effect of overexpression of miR-206 and knockdown of Notch3 on C2C12 cells proliferation, and found that the effect was produced by controlling the transition of G0/G1 and S phase in C2C12 cell cycle. In summary, our results provide direct evidences that miR-206 regulates skeletal muscle cells proliferation and cell cycle arrest partly by targeting the Notch3 gene, which strengthens our understanding of regulatory mechanisms on miR-206 in skeletal muscle growth and development.

Keywords: Cell cycle; Cell proliferation; Notch3; Skeletal muscle; miR-206.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Proliferation / genetics*
  • Mice
  • MicroRNAs / genetics*
  • Muscle Development / genetics*
  • Muscle, Skeletal / growth & development
  • Myoblasts / cytology
  • Myoblasts / metabolism
  • Receptor, Notch3 / genetics*
  • Signal Transduction

Substances

  • MicroRNAs
  • Mirn206 microRNA, mouse
  • Notch3 protein, mouse
  • Receptor, Notch3