miR-200c regulates endothelin-1 induced PASMCs abnormal proliferation and apoptosis

IUBMB Life. 2017 Nov;69(11):877-886. doi: 10.1002/iub.1686. Epub 2017 Oct 16.

Abstract

miR-200c is an antioncogene in multiple tumors. However, its function in the pathogenesis of pulmonary arterial hypertension (PAH) has not been thoroughly investigated nor understood. In this study, we discovered that miR-200c was able to substantially upregulate in pulmonary arterial smooth muscle cells (PASMCs) treated with endothelin-1 (ET-1). miR-200c also induced cell proliferation and suppressed cell apoptosis in PASMCs in vitro. However, miR-200c had no effect on G1/S/G2 transitions during the cell cycle. Furthermore, we identified miR-200c as a new regulator of the microtubule associated protein 2 (MAP-2) and zinc finger E-box binding homeobox1 (ZEB-1) in PASMCs. miR-200c inhibited MAP-2 and ZEB-1 expression by directly binding to their 3'-untranslated regions(3'UTR) according to luciferase assay results. Our findings provide novel insights into the mechanisms of PAH pathogenesis and potential molecular biomarkers for PAH diagnosis and treatment. © 2017 IUBMB Life, 69(11):877-886, 2017.

Keywords: 3′-untranstated region; apoptosis; miR-200c; proliferation; pulmonary arterial hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis / drug effects
  • Binding Sites
  • Cell Hypoxia
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Endothelin-1 / genetics*
  • Endothelin-1 / metabolism
  • Endothelin-1 / pharmacology
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Humans
  • Hypertension, Pulmonary / genetics
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / pathology
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Models, Biological
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pulmonary Artery / cytology
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / metabolism
  • Signal Transduction
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • 3' Untranslated Regions
  • Endothelin-1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MAP2 protein, human
  • MIRN200 microRNA, human
  • MIRN513A1 microRNA, human
  • MIRN628 microRNA, human
  • MIRN663 microRNA, human
  • MicroRNAs
  • Microtubule-Associated Proteins
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1