title: MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2.
abstract: Obesity is characterized by excessive adipose tissue mass and associated with type 2 diabetes and cardiovascular diseases. To fight obesity and its sequels, elucidating molecular events that govern adipocyte differentiation and function is of key importance. MicroRNAs (miRNAs) are a novel class of non-coding, regulatory RNAs that have been shown to regulate crucial cellular processes, including differentiation. Several studies have already assigned miRNAs to distinct functions in murine adipocyte differentiation but only a few studies did so for humans.  Here, we investigated the function of miR-30c in human adipogenesis. miR-30c expression was increased during adipogenesis of human multipotent adipose-derived stem (hMADS) cells, and miR-30c overexpression enforced adipocyte marker gene induction and triglyceride accumulation. miRNA target prediction revealed two putative direct targets of miR-30c, PAI-1 (SERPINE1) and ALK2 (ACVR1, ACTRI), both inversely regulated to miR-30c during adipogenesis and responsive to miR-30c overexpression. Luciferase reporter assays confirmed PAI-1 and ALK2 as direct miR-30c targets. Moreover, reciprocal expression between miR-30c and PAI-1 could also be demonstrated in white adipose tissue of obesity mouse models, suggesting a potential physiological role of miR-30c for PAI-1 regulation in the obese state. Validating PAI-1 and ALK-2 as miR-30c mediators in adipogenesis revealed that not single silencing of PAI-1 or ALK2, but only co-silencing of both phenocopied the pro-adipogenic miR-30c effect. Thus, miR-30c can target two, so far not interconnected genes in distinct pathways, supporting the idea that miRNAs might coordinate larger regulatory networks than previously anticipated.
authors: Institute for Genomics and Bioinformatics, Graz University of Technology, Graz, Austria.
authors: Michael
authors: M
authors: Karbiener
authors: Claudia
authors: C
authors: Neuhold
authors: Peter
authors: P
authors: Opriessnig
authors: Andreas
authors: A
authors: Prokesch
authors: Juliane G
authors: JG
authors: Bogner-Strauss
authors: Marcel
authors: M
authors: Scheideler
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D039902:Multipotent Stem Cells / Q000378:metabolism; D009765:Obesity; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D034741:RNA, Small Interfering; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I