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

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

Author information

1
Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2
Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
3
CNRS, Inserm, iBV, Université Côte d'Azur, Nice, 06107, France.
4
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.
5
Faculty of Medicine, Division of Obstetrics and Gynecology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
6
Faculty of Pharmacy, Department of Pharmaceutical Biotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
7
Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.

KEYWORDS:

APOPTOSIS; CDK9; IN VITRO DIFFERENTIATION; MYOCYTE PROGENITOR; PROLIFERATION; microRNA

PMID:
28608935
DOI:
10.1002/jcb.26213
[Indexed for MEDLINE]

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