Cyclic stretch induced miR-146a upregulation delays C2C12 myogenic differentiation through inhibition of Numb

Proliferation and differentiation of muscle stem cells must be tightly regulated by intrinsic and extrinsic signals for effective regeneration and adaptive response. MicroRNAs have been implicated as potent regulators in diverse biological processes at the level of posttranscriptional repression. In...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-01, Vol.378 (2), p.259-263
Main Authors: Kuang, Wei, Tan, Jiali, Duan, Yinzhong, Duan, Jianmin, Wang, Weijian, Jin, Fang, Jin, Zuolin, Yuan, Xiao, Liu, Yanpu
Format: Article
Language:English
Subjects:
3' Untranslated Regions - antagonists & inhibitors
3' Untranslated Regions - genetics
60 APPLIED LIFE SCIENCES
Animals
Base Sequence
CELL DIFFERENTIATION
Cell Line
INHIBITION
Membrane Proteins - antagonists & inhibitors
Membrane Proteins - genetics
Mice
MicroRNAs - antagonists & inhibitors
MicroRNAs - genetics
MicroRNAs - physiology
miR-146a
Muscle Development
MUSCLES
Myogenic differentiation
Nerve Tissue Proteins - antagonists & inhibitors
Nerve Tissue Proteins - genetics
Numb
PROLIFERATION
REGENERATION
SIGNALS
STEM CELLS
Up-Regulation
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Summary:Proliferation and differentiation of muscle stem cells must be tightly regulated by intrinsic and extrinsic signals for effective regeneration and adaptive response. MicroRNAs have been implicated as potent regulators in diverse biological processes at the level of posttranscriptional repression. In this study, we found that miR-146a was significantly upregulated upon a 48-h cyclic stretch of 5% elongation/10cycles/min. Importantly, miR-146 was predicted to base-pair with sequences in the 3′ UTR of Numb, which promotes satellite cell differentiation towards muscle cells by inhibiting Notch signaling. Through reporter assay and exogenous expression experiment, we confirmed Numb was inhibited by miR-146a. Inhibition of miR-146a by antago-miR-146a rescued the expression of Numb and facilitated the differentiation of C2C12 at a cost of compromised proliferation. Thus, for the first time, we propose a role of miR-146a in skewing the balance of muscle differentiation and proliferation through inhibiting the expression of Numb.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.11.041