title: miR-127 enhances myogenic cell differentiation by targeting S1PR3.
abstract: MicroRNAs (miRNAs) have recently been implicated in muscle stem cell function. miR-127 is known to be predominantly expressed in skeletal muscle, but its roles in myogenic differentiation and muscle regeneration are unknown. Here, we show that miR-127 is upregulated during C2C12 and satellite cell (SC) differentiation and, by establishing C2C12 cells stably expressing miR-127, demonstrate that overexpression of miR-127 in C2C12 cells enhances myogenic cell differentiation. To investigate the function of miR-127 during muscle development and regeneration in vivo, we generated miR-127 transgenic mice. These mice exhibited remarkably accelerated muscle regeneration compared with wild-type mice by promoting SC differentiation. Mechanistically, we demonstrated that the gene encoding sphingosine-1-phosphate receptor 3 (S1PR3), a G-protein-coupled receptor for sphingosine-1-phosphate, is a target of miR-127 required for its function in promoting myogenic cell differentiation. Importantly, overexpression of miR-127 in muscular dystrophy model mdx mice considerably ameliorated the disease phenotype. Thus, our findings suggest that miR-127 may serve as a potential therapeutic target for the treatment of skeletal muscle disease in humans.
authors.affiliation: The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhai
authors.affiliation: The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China.
authors.forename: Rimao
authors.initials: R
authors.lastname: Wu
authors.affiliation: The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China.
authors.forename: Wanhong
authors.initials: W
authors.lastname: Han
authors.affiliation: The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China.
authors.forename: Dahai
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D051379:Mice; D018101:Mice, Inbred mdx; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis / Q000235:genetics; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism*; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: D035683:MicroRNAs; C533109:Mirn127 microRNA, mouse; D049349:Receptors, Lysosphingolipid; C501285:S1pr3 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors