Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid

Karbiener, M; Neuhold, C; Opriessnig, P; Prokesch, A; Bogner-Strauss, JG; Scheideler, M.
MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2.
RNA Biol. 2011; 8(5):850-860 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Karbiener Michael
Prokesch Andreas

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Plum Analytics:
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.
Find related publications in this database (using NLM MeSH Indexing)
Activin Receptors, Type I - genetics Activin Receptors, Type I - metabolism
Adipocytes - cytology Adipocytes - metabolism
Adipogenesis - genetics
Adipose Tissue, White - metabolism
Animals -
Cell Differentiation -
Cell Line -
Humans -
Mesenchymal Stromal Cells - metabolism
Mice -
Mice, Obese -
Mice, Transgenic -
MicroRNAs - genetics MicroRNAs - metabolism
Multipotent Stem Cells - metabolism
Obesity -
Plasminogen Activator Inhibitor 1 - genetics Plasminogen Activator Inhibitor 1 - metabolism
RNA Interference -
RNA, Small Interfering -

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