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

First Author  Kuang W Year  2009
Journal  Biochem Biophys Res Commun Volume  378
Issue  2 Pages  259-63
PubMed ID  19026611 Mgi Jnum  J:143068
Mgi Id  MGI:3822714 Doi  10.1016/j.bbrc.2008.11.041
Citation  Kuang W, et al. (2009) Cyclic stretch induced miR-146a upregulation delays C2C12 myogenic differentiation through inhibition of Numb. Biochem Biophys Res Commun 378(2):259-63
abstractText  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.
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