Transforming growth factor-beta-regulated miR-24 promotes skeletal muscle differentiation.
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.
Sun
Qiang
Q
State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, 20 Dongdajie, Beijing 100071, PR China.
Zhang
Yan
Y
Yang
Guang
G
Chen
Xiaoping
X
Zhang
Yingai
Y
Cao
Guojun
G
Wang
Jian
J
Sun
Yanxun
Y
Zhang
Peng
P
Fan
Ming
M
Shao
Ningsheng
N
Yang
Xiao
X
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051900:Smad3 Protein / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D053773:Transforming Growth Factor beta1