title: miR-29 targets Akt3 to reduce proliferation and facilitate differentiation of myoblasts in skeletal muscle development.
abstract: MicroRNAs (miRNAs) are a type of endogenous noncoding small RNAs involved in the regulation of multiple biological processes. Recently, miR-29 was found to participate in myogenesis. However, the underlying mechanisms by which miR-29 promotes myogenesis have not been identified. We found here that miR-29 was significantly upregulated with age in postnatal mouse skeletal muscle and during muscle differentiation. Overexpression of miR-29 inhibited mouse C2C12 myoblast proliferation and promoted myotube formation. miR-29 specifically targeted Akt3, a member of the serine/threonine protein kinase family responsive to growth factor cell signaling, to result in its post-transcriptional downregulation. Furthermore, knockdown of Akt3 by siRNA significantly inhibited the proliferation of C2C12 cells, and conversely, overexpression of Akt3 suppressed their differentiation. Collectively and given the inverse endogenous expression pattern of rising miR-29 levels and decreasing Akt3 protein levels with age in mouse skeletal muscle, we propose a novel mechanism in which miR-29 modulates growth and promotes differentiation of skeletal muscle through the post-transcriptional downregulation of Akt3.
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, PRC.
authors.forename: W
authors.initials: W
authors.lastname: Wei
authors.forename: H-B
authors.initials: HB
authors.lastname: He
authors.forename: W-Y
authors.initials: WY
authors.lastname: Zhang
authors.forename: H-X
authors.initials: HX
authors.lastname: Zhang
authors.forename: J-B
authors.initials: JB
authors.lastname: Bai
authors.forename: H-Z
authors.initials: HZ
authors.lastname: Liu
authors.forename: J-H
authors.initials: JH
authors.lastname: Cao
authors.forename: K-C
authors.initials: KC
authors.lastname: Chang
authors.forename: X-Y
authors.initials: XY
authors.lastname: Li
authors.forename: S-H
authors.initials: SH
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D017124:Conserved Sequence; D004794:Enzyme Repression; D015870:Gene Expression; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D032446:Myoblasts / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C491753:Akt3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt