MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1

Cell Physiol Biochem. 2017;42(2):780-796. doi: 10.1159/000478069. Epub 2017 Jun 19.

Abstract

Background/aims: Mesenchymal stem cells (MSCs) play an important role in regulating angiogenesis and immune balance. Abnormal proliferation and function of MSCs were reported at maternal fetal interface in patients with pre-eclampsia (PE). Micro-RNA-495 was known to be upregulated in the MSCs derived from patients with PE. However, it is not clear whether the up-regulated miR-495 is related to the pathogenesis of PE.

Methods: We analyzed the expression of miR-495 in MSCs and umbilical cords derived from healthy pregnancies (NC) and PE, then we upregulated or downregulated the expression of miR-495 in MSCs derived from NC and tested the proliferation, apoptosis, migration, invasion, tube formation and senescence.

Results: In the current study, we found that the expression of miR-495 was significantly increased in both umbilical cord tissues and MSCs in patients with severe PE. Overexpressing miR-495 arrested cell cycle in S phase and promoted cell apoptosis. The supernatants from miR-495-overexpressed-MSCs inhibited the migration of MSCs and HTR-8/SVneo, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-miR-495 had the opposite effects. Furthermore, we analyzed the senescence related β-galactosidase activity and CD146 and found that miR-495 induced the senescence of MSCs. Molecular mechanism studies confirmed that Bmi-1 mediated these effects of miR-495 on MSCs.

Conclusion: Taken together, our data demonstrated that miR-495 induced senescence of MSCs may be involved in the pathogenesis of PE.

Keywords: Bmi-1; MSC; MiR-495; Preeclampsia; Senescence.

MeSH terms

  • Adult
  • Aging / genetics*
  • Apoptosis / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Polycomb Repressive Complex 1 / genetics*
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Umbilical Cord / metabolism

Substances

  • BMI1 protein, human
  • MIRN495 microRNA, human
  • MicroRNAs
  • Polycomb Repressive Complex 1