title: miR-125a-3p and miR-483-5p promote adipogenesis via suppressing the RhoA/ROCK1/ERK1/2 pathway in multiple symmetric lipomatosis.
abstract: Multiple symmetric lipomatosis (MSL) is a rare disease characterized by symmetric and abnormal distribution of subcutaneous adipose tissue (SAT); however, the etiology is largely unknown. We report here that miR-125a-3p and miR-483-5p are upregulated in the SAT of MSL patients, promoting adipogenesis through suppressing the RhoA/ROCK1/ERK1/2 pathway. TaqMan microRNA (miR) array analysis revealed that 18 miRs were upregulated in the SAT of MSL patients. Transfection of human adipose-derived mesenchymal stem cells (hADSCs) with the individual agomirs of these 18 miRs showed that miR-125a-3p and miR-483-5p significantly promoted adipogenesis. A dual-luciferase assay showed that RhoA and ERK1 were the targets of miR-125a-3p and miR-483-5p, respectively. Moreover, transfection of hADSCs with mimics of miR-125a-3p and miR-483-5p resulted in a pronounced decrease of ERK1/2 phosphorylation in the nucleus; conversely, transfection of hADSCs with inhibitors of miR-125a-3p and miR-483-5p led to a significant increase of ERK1/2 phosphorylation in the nucleus. Most importantly, we found that miR-125a-3p and miR-483-5p promoted de novo adipose tissue formation in nude mice. These results demonstrated that miR-125a-3p and miR-483-5p coordinately promoted adipogenesis through suppressing the RhoA/ROCK1/ERK1/2 pathway. Our findings may provide novel strategies for the management and treatment of MSL or obesity.
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
authors.forename: Honghui
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Mo
mesh_terms: D020413:3' Untranslated Regions; D050156:Adipogenesis; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D008069:Lipomatosis, Multiple Symmetrical / Q000235:genetics* / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010766:Phosphorylation; D050151:Subcutaneous Fat / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020742:rhoA GTP-Binding Protein