title: MicroRNA-432 targeting E2F3 and P55PIK inhibits myogenesis through PI3K/AKT/mTOR signaling pathway.
abstract: Skeletal muscle is the dominant executant in locomotion and regulator in energy metabolism. Embryonic myogenesis and postnatal muscle growth are controlled by a cascade of transcription factors and epigenetic regulatory mechanisms. MicroRNAs (miRNAs), a family of non-coding RNA of 22 nucleotides in length, post-transcriptionally regulates expression of mRNA by pairing the seed sequence to 3' UTR of target mRNA. Increasing evidence has demonstrated that miRNAs are important regulators in diverse myogenic processes. The profiling of miRNA expression revealed that miR-432 is more enriched in the longissimus dorsi of 35-day-old piglets than that of adult pigs. Our gain of function study showed that miR-432 can negatively regulate both myoblast proliferation and differentiation. Mechanically, we found that miR-432 is able to down-regulate E2F transcription factor 3 (E2F3) to inactivate the expression of cell cycle and myogenic genes. We also identified that phosphatidylinositol 3-kinase regulatory subunit (P55PIK) is another target gene of miR-432 in muscle cells. downregulation of P55PIK by miR-432 leads to inhibition of P55PIK-mediated PI3K/AKT/mTOR signaling pathway during differentiation. The blocking effect of miR-432 on this pathway can be rescued by insulin treatment. Taken together, our findings identified microRNA-432 as a potent inhibitor of myogenesis which functions by targeting E2F3 and P55PIK in muscle cells.
authors.affiliation: a Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University , Yangling, Shaanxi , China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Ma
authors.affiliation: a Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University , Yangling, Shaanxi , China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University , Yangling, Shaanxi , China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Chen
authors.affiliation: a Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University , Yangling, Shaanxi , China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cai
authors.affiliation: a Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University , Yangling, Shaanxi , China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Chen
authors.affiliation: a Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University , Yangling, Shaanxi , China.
authors.forename: Wuzi
authors.initials: W
authors.lastname: Dong
authors.affiliation: a Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University , Yangling, Shaanxi , China.
authors.forename: Gongshe
authors.initials: G
authors.lastname: Yang
authors.affiliation: a Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University , Yangling, Shaanxi , China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Pang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D016000:Cluster Analysis; D050699:E2F3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D024510:Muscle Development / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013552:Swine; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D050699:E2F3 Transcription Factor; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: E2F3; P55PIK; PI3K/Akt/mTOR pathway; microRNA-432; myogenesis