Reverse the down regulation of miR-92b-3p by hypoxia can suppress the proliferation of pulmonary artery smooth muscle cells by targeting USP28

Biochem Biophys Res Commun. 2018 Sep 18;503(4):3064-3077. doi: 10.1016/j.bbrc.2018.08.095. Epub 2018 Aug 24.

Abstract

MiR-92b-3p has been shown to take part in several disease by regulate proliferation, apoptosis, differentiation and metastasis. However, the role of miR-92b-3p in pulmonary arterial hypertension (PAH) has not been illustrated clearly. Here, we found the level of miR-92b-3p which mainly located in the smooth muscle layer was down-regulation under hypoxic condition. It can inhibit pulmonary artery smooth muscle cells (PASMCs) proliferation and cell cycle progression. Through luciferase assay, miR-92b-3p bound to the 3'-UTR of USP28. we found that there was a significant negative relation between the level of miR-92b-3p and USP28 at protein level and reversed the down regulation of miR-92b-3p by hypoxia can suppress the proliferation of pulmonary artery smooth muscle cells by targeting USP28. These results suggested that miR-92b-3p acted a potential proliferation regulator in PASMCs and it maybe a novel treatment target of PAH.

Keywords: Cell proliferation; Hypoxia; MiR-92b-3p; Pulmonary arterial hypertension; USP28.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Hypoxia
  • Cell Proliferation*
  • Cells, Cultured
  • Down-Regulation
  • Hypertension, Pulmonary / genetics
  • Hypoxia / genetics*
  • Male
  • MicroRNAs / genetics*
  • Myocytes, Smooth Muscle / cytology*
  • Myocytes, Smooth Muscle / metabolism
  • Pulmonary Artery / cytology*
  • Pulmonary Artery / metabolism
  • Rats, Wistar
  • Ubiquitin-Specific Proteases / genetics*
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • MIRN92 microRNA, rat
  • MicroRNAs
  • Ubiquitin-Specific Proteases
  • Usp28 protein, rat