miR-181a modulates circadian rhythm in immortalized bone marrow and adipose derived stromal cells and promotes differentiation through the regulation of PER3

Sci Rep. 2019 Jan 22;9(1):307. doi: 10.1038/s41598-018-36425-w.

Abstract

miRNAs are important regulators of diverse cellular processes including proliferation, apoptosis, and differentiation. In the context of bone marrow derived stromal cell and adipose derived stromal cell differentiation, miRNAs are established regulators of both differentiation or stemness depending on their target. Furthermore, miRNA dysregulation can play a key role in various disease states. Here we show that miR-181a is regulated in a circadian manner and is induced during both immortalized bone marrow derived stromal cell (iBMSC) as well as primary patient adipose derived stromal cell (PASC) adipogenesis. Enhanced expression of miR-181a in iBMSCs and PASCs produced a robust increase in adipogenesis through the direct targeting of the circadian factor period circadian regulator 3 (PER3). Furthermore, we show that knocking down endogenous miR-181a expression in iBMSC has a profound inhibitory effect on iBMSC adipogenesis through its regulation of PER3. Additionally, we found that miR-181a regulates the circadian dependency of the adipogenesis master regulator PPARγ. Taken together, our data identify a previously unknown functional link between miR-181a and the circadian machinery in immortalized bone marrow stromal cells and adipose derived stromal cells highlighting its importance in iBMSC and ASC adipogenesis and circadian biology.

MeSH terms

  • Adipogenesis
  • Adipose Tissue / cytology
  • Animals
  • Bone Marrow Cells / cytology
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cells, Cultured
  • Circadian Rhythm / drug effects*
  • Humans
  • MicroRNAs / pharmacology
  • MicroRNAs / physiology*
  • Period Circadian Proteins / drug effects
  • Period Circadian Proteins / physiology*
  • Stromal Cells / metabolism*

Substances

  • MIrn181 microRNA, human
  • MicroRNAs
  • PER3 protein, human
  • Period Circadian Proteins