miR-146b-5p regulates bone marrow mesenchymal stem cell differentiation by SIAH2/PPARγ in aplastic anemia children and benzene-induced aplastic anemia mouse model

Cell Cycle. 2020 Oct;19(19):2460-2471. doi: 10.1080/15384101.2020.1807081. Epub 2020 Aug 25.

Abstract

This study aimed to reveal the mechanism of miR-146b-5p in the differentiation of bone marrow mesenchymal stem cells (BMSCs) derived from children with aplastic anemia (AA). Here, we found that miR-146b-5p was highly expressed in BMSCs from children with AA, and the BMSCs surface markers expressions in BMSCs derived from children with AA and the healthy controls exerted no significant differences. Besides, the overexpression of miR-146b-5p in normal human-derived BMSCs promoted the adipogenic differentiation of BMSCs. Furthermore, miR-146b-5p negatively regulated SIAH2 luciferase activity, and the interference with miR-146b-5p reduced the stability of PPARγ protein and inhibited SIAH2-mediated ubiquitination of PPARγ protein. Besides, the interference with miR-146b-5p was beneficial for ameliorating AA in a mouse model of AA. Overall, our results found that miR-146b-5p was highly expressed in BMSCs from children with AA, and our further studies indicated that miR-146b-5p improved AA via promoting SIAH2-mediated ubiquitination of PPARγ protein.

Keywords: Aplastic anemia; BMSCs; PPARγ; SIAH2; miR-146b-5p.

MeSH terms

  • Adipogenesis*
  • Adolescent
  • Anemia, Aplastic / chemically induced
  • Anemia, Aplastic / genetics
  • Anemia, Aplastic / metabolism*
  • Anemia, Aplastic / pathology
  • Animals
  • Benzene
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / pathology
  • Case-Control Studies
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Signal Transduction
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination

Substances

  • MIRN146 microRNA, human
  • MicroRNAs
  • Mirn146 microRNA, mouse
  • Nuclear Proteins
  • PPAR gamma
  • PPARG protein, human
  • Pparg protein, mouse
  • Siah2 protein, mouse
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins
  • Benzene