MicroRNA-214 promotes myogenic differentiation by facilitating exit from mitosis via down-regulation of proto-oncogene N-ras.
Vertebrate muscle differentiation is coordinated by an intricate network of transcription factors requiring proliferating myogenic precursors to withdraw irreversibly from the cell cycle. Recent studies have implicated a large number of microRNAs exerting another layer of control in many aspects of muscle differentiation. By annealing to short recognition sequences in the 3'-untranslated region, microRNAs attenuate target gene expression through translation repression or mRNA degradation. Here, we show that miR-214 promotes myogenic differentiation in mouse C2C12 myoblasts at a step preceding the induction of p21 and myogenin. Blocking miR-214 function with a 2'-O-methylated double-stranded inhibitor maintained C2C12 cells in the active cell cycle, thereby inhibiting the myogenic differentiation. By global gene expression profiling, we identified the proto-oncogene N-ras as one of miR-214 targets. Furthermore, manipulating the N-Ras level with small interfering RNA or adenovirus-mediated forced expression either augmented or attenuated the effect of miR-214, respectively. Thus, our data uncovered a novel microRNA-mediated mechanism that controls myogenic differentiation.
Liu
Jun
J
Department of Developmental Genetics, Center for Cancer Research, and Center for Regenerative Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Luo
Xiao-Ju
XJ
Xiong
An-Wen
AW
Zhang
Zeng-di
ZD
Yue
Shen
S
Zhu
Ming-Sheng
MS
Cheng
Steven Y
SY
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D011905:Genes, ras; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D008938:Mitosis; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology*
D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse