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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2.
RNA Biol. 8, 850-860 (2011)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2011
HGF-reported in Year
0
ISSN (print) / ISBN
1547-6286
e-ISSN
1555-8584
Journal
RNA Biology
Quellenangaben
Volume: 8,
Issue: 5,
Pages: 850-860
Publisher
Landes Bioscience
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Cancer (IDC)
PubMed ID
21878751
Erfassungsdatum
2011-12-31