Transforming growth factor-beta-regulated miR-24 promotes skeletal muscle differentiation

Nucleic Acids Res. 2008 May;36(8):2690-9. doi: 10.1093/nar/gkn032. Epub 2008 Mar 19.


MicroRNAs (miRNAs) have recently been proposed as a versatile class of molecules involved in regulation of a variety of biological processes. However, the role of miRNAs in TGF-beta-regulated biological processes is poorly addressed. In this study, we found that miR-24 was upregulated during myoblast differentiation and could be inhibited by TGF-beta1. Using both a reporter assay and Northern blot analysis, we showed that TGF-beta1 repressed miR-24 transcription which was dependent on the presence of Smad3 and a Smads binding site in the promoter region of miR-24. TGF-beta1 was unable to inhibit miR-24 expression in Smad3-deficient myoblasts, which exhibited accelerated myogenesis. Knockdown of miR-24 led to reduced expression of myogenic differentiation markers in C2C12 cells, while ectopic expression of miR-24 enhanced differentiation, and partially rescued inhibited myogenesis by TGF-beta1. This is the first study demonstrating a critical role for miRNAs in modulating TGF-beta-dependent inhibition of myogenesis, and provides a novel mechanism of the genetic regulation of TGF-beta signaling during skeletal muscle differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Differentiation
  • Cells, Cultured
  • Gene Expression Regulation
  • Mice
  • Mice, Knockout
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Muscle, Skeletal / cytology*
  • Myoblasts, Skeletal / cytology
  • Myoblasts, Skeletal / drug effects
  • Myoblasts, Skeletal / metabolism*
  • Promoter Regions, Genetic
  • Smad3 Protein / genetics
  • Smad3 Protein / physiology
  • Transcription, Genetic
  • Transforming Growth Factor beta1 / pharmacology*


  • MicroRNAs
  • Mirn24 microRNA, mouse
  • Smad3 Protein
  • Smad3 protein, mouse
  • Transforming Growth Factor beta1