title: MicroRNA-128 targets myostatin at coding domain sequence to regulate myoblasts in skeletal muscle development.
abstract: MicroRNAs (miRNAs or miRs) play a critical role in skeletal muscle development. In a previous study we observed that miR-128 was highly expressed in skeletal muscle. However, its function in regulating skeletal muscle development is not clear. Our hypothesis was that miR-128 is involved in the regulation of the proliferation and differentiation of skeletal myoblasts. In this study, through bioinformatics analyses, we demonstrate that miR-128 specifically targeted mRNA of myostatin (MSTN), a critical inhibitor of skeletal myogenesis, at coding domain sequence (CDS) region, resulting in down-regulating of myostatin post-transcription. Overexpression of miR-128 inhibited proliferation of mouse C2C12 myoblast cells but promoted myotube formation; whereas knockdown of miR-128 had completely opposite effects. In addition, ectopic miR-128 regulated the expression of myogenic factor 5 (Myf5), myogenin (MyoG), paired box (Pax) 3 and 7. Furthermore, an inverse relationship was found between the expression of miR-128 and MSTN protein expression in vivo and in vitro. Taken together, these results reveal that there is a novel pathway in skeletal muscle development in which miR-128 regulates myostatin at CDS region to inhibit proliferation but promote differentiation of myoblast cells.
authors.affiliation: Institute of Swine Science, Nanjing Agricultural University, Nanjing 210095, China; Huaian Academy of Nanjing Agricultural University, Huaian 223001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Institute of Swine Science, Nanjing Agricultural University, Nanjing 210095, China; Huaian Academy of Nanjing Agricultural University, Huaian 223001, China. Electronic address: zhoubo@njau.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Institute of Swine Science, Nanjing Agricultural University, Nanjing 210095, China; Huaian Academy of Nanjing Agricultural University, Huaian 223001, China.
authors.forename: Pinghua
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907-2054, USA.
authors.forename: Allan P
authors.initials: AP
authors.lastname: Schinckel
authors.affiliation: Institute of Swine Science, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liang
authors.affiliation: Institute of Swine Science, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Swine Science, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Huizhi
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Swine Science, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Fu
authors.affiliation: Institute of Swine Science, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Qingpo
authors.initials: Q
authors.lastname: Chu
authors.affiliation: Institute of Swine Science, Nanjing Agricultural University, Nanjing 210095, China; Huaian Academy of Nanjing Agricultural University, Huaian 223001, China. Electronic address: rhhuang@njau.edu.cn.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Huang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D055435:Myostatin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; C550324:Mirn128 microRNA, mouse; C525912:Mstn protein, mouse; D009124:Muscle Proteins; D055435:Myostatin
keywords: C2C12 myoblasts; MicroRNA-128; Myostatin; Proliferation and differentiation