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 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.
Kuang
Wei
W
Department of Oral and Maxillofacial Surgery, College of Stomatology, The Fourth Military Medical University, No. 145 Changlexi Road, Xi'an, Shaanxi Province 710032, People's Republic of China.
Tan
Jiali
J
Duan
Yinzhong
Y
Duan
Jianmin
J
Wang
Weijian
W
Jin
Fang
F
Jin
Zuolin
Z
Yuan
Xiao
X
Liu
Yanpu
Y
D020413:3' Untranslated Regions / Q000037:antagonists & inhibitors / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D024510:Muscle Development; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D015854:Up-Regulation
D020413:3' Untranslated Regions; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse