miR-377-3p regulates adipogenic differentiation of human bone marrow mesenchymal stem cells by regulating LIFR

Mol Cell Biochem. 2018 Dec;449(1-2):295-303. doi: 10.1007/s11010-018-3366-0. Epub 2018 Jun 29.

Abstract

MicroRNAs are members of the family of non-coding small RNAs that regulate gene expression either by inhibiting mRNA translation or by promoting mRNA degradation at the post-transcriptional level. They play an important role in the differentiation of human bone marrow mesenchymal stem cells (hMSCs) into adipocytes. However, the role of microRNAs in this process remains to be poorly understood. Here, we observed that miR-377-3p expression was markedly decreased during adipogenic differentiation of hMSCs. Overexpression of miR-377-3p decreased adipocyte differentiation and downregulated the expression of adipogenic markers. Meanwhile, bioinformatics-based studies suggested that LIFR is a target of miR-377-3p. Further analysis confirmed that expression of LIFR present markedly increased during adipogenic differentiation of hMSCs. In addition, downregulation expression of LIFR significantly inhibited the process of adipocyte differentiation. To confirm the relation between miR-377-3p and LIFR, luciferase reporter assays were carried out. The results indicated that miR-377-3p bound directly to the 3'-untranslated region of LIFR. These data indicate that miR-377-3p suppressed adipogenesis of hMSCs by targeting LIFR, which provides novel insights into the molecular mechanism of miRNA-mediated cellular differentiation.

Keywords: Adipogenic differentiation; Human bone marrow mesenchymal stem cells; Leukemia inhibitory factor receptor; miR-377-3p.

MeSH terms

  • 3' Untranslated Regions
  • Adipogenesis*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Cell Differentiation*
  • Cell Line
  • Humans
  • Leukemia Inhibitory Factor Receptor alpha Subunit / biosynthesis*
  • Leukemia Inhibitory Factor Receptor alpha Subunit / genetics
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*

Substances

  • 3' Untranslated Regions
  • LIFR protein, human
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • MIRN377 microRNA, human
  • MicroRNAs