Down-regulation of lncRNA MEG3 promotes hypoxia-induced human pulmonary artery smooth muscle cell proliferation and migration via repressing PTEN by sponging miR-21

Biochem Biophys Res Commun. 2018 Jan 15;495(3):2125-2132. doi: 10.1016/j.bbrc.2017.11.185. Epub 2017 Dec 2.

Abstract

Hypoxia-induced pulmonary hypertension is a life-threatening disease arising from a progressive increase in pulmonary vascular resistance, irreversible pulmonary vascular remodeling and resulting in right ventricular failure. Recent studies suggested that pulmonary artery smooth muscle cell proliferation and migration played an important role in the pathogenesis of hypoxia-induced pulmonary hypertension. However, the mechanisms of hypoxia-induced pulmonary hypertension are complicated and largely unclear. In this study, we discovered that lncRNA MEG3 was down-regulated in human pulmonary artery smooth muscle cell in hypoxia, and inhibition of MEG3 promoted the cell proliferation and cell migration in both normal and hypoxia condition. Further study demonstrated that MEG3 exerted its function via regulation of miR-21 expression in both normal and hypoxia condition. In addition, we displayed the modulation of PTEN by miR-21 and their role in hypoxia. Ultimately, our study illustrated that MEG3 exerts its role via miR-21/PTEN axis in human pulmonary artery smooth muscle cell under both normal and hypoxia conditions.

Keywords: Competing endogenous RNA; Hypoxia-induced pulmonary hypertension; Pulmonary artery smooth muscle cells; lncRNA MEG3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia / physiology*
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Down-Regulation / physiology
  • Humans
  • MicroRNAs / metabolism*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / physiology*
  • PTEN Phosphohydrolase / metabolism*
  • Pulmonary Artery / cytology
  • Pulmonary Artery / physiology*
  • RNA, Long Noncoding / metabolism*

Substances

  • MEG3 non-coding RNA, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • PTEN Phosphohydrolase
  • PTEN protein, human