MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2

RNA Biol. Sep-Oct 2011;8(5):850-60. doi: 10.4161/rna.8.5.16153. Epub 2011 Aug 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 Stem 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

Substances

  • MIRN30b microRNA, human
  • MicroRNAs
  • Plasminogen Activator Inhibitor 1
  • RNA, Small Interfering
  • ACVR1 protein, human
  • Activin Receptors, Type I