title: Regulatory Axis of miR-195/497 and HMGA1-Id3 Governs Muscle Cell Proliferation and Differentiation.
abstract: Myocytes withdraw from the cell cycle to differentiate during muscle development. Given the capacity of microRNAs (miRNAs) to regulate gene expression during development, we screened for miRNAs that were associated with muscle development. S-Poly(T) Plus analysis of 273 miRNAs in porcine longissimus dorsi muscles revealed 14 miRNAs that were strongly upregulated with age of postnatal muscle developmentin vivo, including miR-195 and miR-497. These two miRNAs were also strongly upregulated at late differentiation stages of mouse skeletal myoblast C2C12 cells, and demethylation treatment induced significant upregulation of miR-195/497. Manipulation of miR-195/497 expression resulted in dramatic changes in the proliferation and differentiation of C2C12 cells. We identified high-mobility group AT-hook 1 (Hmga1) mRNA as a highly conserved target of miR-195/497 in C2C12 myoblasts. Overexpression of miR-195/497 orHmga1silencing in C2C12 cells promoted myogenic differentiation. Moreover, we showed that miR-195/497 repressedHmga1, which in turn downregulated one of the HMGA1 downstream targetsId3, whose inhibitory effect on myogenic differentiation is well established. Our study revealed a subset of potential development-associated miRNAs and suggests a novel regulatory axis for myogenesis in which miR-195/497 promote myogenic differentiation by repressing the HMGA1-Id3 pathway.
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Physiology, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518000, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Kang
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Deming
authors.initials: D
authors.lastname: Gou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology*; D024003:HMGA Proteins / Q000235:genetics / Q000378:metabolism*; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
chemical_list: D020413:3' Untranslated Regions; D024003:HMGA Proteins; C552722:MIRN195 microRNA, human; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D025741:HMGA1a Protein
keywords: Hmga1; differentiation; miR-195/497; myoblast; proliferation.; skeletal muscle