The microRNA miR-124 inhibits vascular smooth muscle cell proliferation by targeting S100 calcium-binding protein A4 (S100A4)

FEBS Lett. 2017 Apr;591(7):1041-1052. doi: 10.1002/1873-3468.12606. Epub 2017 Mar 19.

Abstract

S100 calcium-binding protein A4 (S100A4) induces proliferation and migration of vascular smooth muscle cells (VSMCs). We aimed to find the microRNA regulating S100A4 expression. S100A4 transcripts are abruptly increased in the acute phase of carotid arterial injury 1 day later (at day 1) but gradually decreases at days 7 and 14. Bioinformatics analysis reveals that miR-124 targets S100A4. VSMC survival is attenuated by miR-124 mimic but increased by miR-124 inhibitor. miR-124 decreases immediately after carotid arterial injury but dramatically increases at days 7 and 14. miR-124 inhibitor-induced cell proliferation is blocked by S100A4 siRNA, whereas miR-124-induced cell death is recovered by S100A4. Our findings suggest that miR-124 is a novel regulator of VSMC proliferation and may play a role in the development of neointimal proliferation.

Keywords: miR-124; S100A4; carotid artery injury; neointima; vascular smooth muscle cell proliferation.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Blotting, Western
  • Carotid Artery Injuries / genetics
  • Carotid Artery Injuries / metabolism
  • Cell Line
  • Cell Proliferation / genetics*
  • Gene Expression Regulation*
  • Immunohistochemistry
  • Male
  • MicroRNAs / genetics*
  • Muscle, Smooth, Vascular / cytology
  • Myocytes, Smooth Muscle / metabolism*
  • Neointima / genetics
  • Neointima / metabolism
  • RNA Interference
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Calcium-Binding Protein A4 / genetics*
  • S100 Calcium-Binding Protein A4 / metabolism
  • Sequence Homology, Amino Acid
  • Time Factors

Substances

  • 3' Untranslated Regions
  • MIRN124 microRNA, rat
  • MicroRNAs
  • S100 Calcium-Binding Protein A4
  • S100a4 protein, rat