CDK9 Regulates Apoptosis of Myoblast Cells by Modulation of microRNA-1 Expression

J Cell Biochem. 2018 Jan;119(1):547-554. doi: 10.1002/jcb.26213. Epub 2017 Jul 11.

Abstract

Cdk9 is the catalytic core of the positive transcription elongation factor b (P-TEFb) and regulates transcriptional elongation factors by phosphorylation of RNA pol II. Apart from its role on myogenic gene expression, Cdk9 regulation of muscle-specific microRNAs in the early stage of cardiomyogenesis is poorly understood. Here we demonstrate that Cdk9 not only regulates myogenic transcription factors, but also controls muscle-specific microRNAs. During cardiac differentiation of mouse embryonic stem cells, high Cdk9 expression preceded up-regulation of miR-1. To investigate potential regulatory roles of Cdk9 on cardiac microRNAs and myogenesis genes, we overexpressed Cdk9 in myoblast C2C12 cells, which resulted in significant induction of miR-1 and miR-206, while miR-133 was downregulated. Moreover, expression levels of MyoD and Srf, key regulators of myogenesis, also increased in cells with overexpression of Cdk9. We further observed Cdk9-mediated apoptosis in C2C12 cells corresponding to induction of miR-1 expression levels. Thus, Cdk9 plays a complex role in myocyte progenitor differentiation and apoptosis by regulating myogenic protein and muscle-specific microRNA expression. J. Cell. Biochem. 119: 547-554, 2018. © 2017 Wiley Periodicals, Inc.

Keywords: APOPTOSIS; CDK9; IN VITRO DIFFERENTIATION; MYOCYTE PROGENITOR; PROLIFERATION; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line
  • Cyclin-Dependent Kinase 9 / genetics
  • Cyclin-Dependent Kinase 9 / metabolism*
  • Gene Expression Regulation*
  • Mice
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Muscle Development*
  • Myoblasts, Cardiac / cytology
  • Myoblasts, Cardiac / metabolism*

Substances

  • MicroRNAs
  • Mirn1 microRNA, mouse
  • Cdk9 protein, mouse
  • Cyclin-Dependent Kinase 9