microRNA-338-3p promotes ox-LDL-induced endothelial cell injury through targeting BAMBI and activating TGF-β/Smad pathway

J Cell Physiol. 2019 Jul;234(7):11577-11586. doi: 10.1002/jcp.27814. Epub 2018 Dec 17.

Abstract

microRNAs (miRNAs) have been revealed to participate in the pathological process of atherosclerosis (AS). However, the exact role of miR-338-3p, a target miRNA of BMP and activin membrane-bound inhibitor (BAMBI), and its possible molecular mechanism in AS remain unidentified. In this study, we found that BAMBI was significantly decreased, whereas miR-338-3p increased in patients with AS and oxidized low-density lipoprotein (ox-LDL)-induced HUVEC cells. Furthermore, overexpression of miR-338-3p significantly decreased cell viability and elevated cell apoptosis, whereas its inhibition significantly promoted cell viability and inhibited cell apoptosis in ox-LDL-induced HUVEC cells. Moreover, miR-338-3p overexpression increased TGF-β/Smad pathway activation in ox-LDL-induced HUVEC cells. A dual-luciferase reporter assay confirmed the direct interaction between miR-338-3p and the 3'-untranslated region of BAMBI messenger RNA. Furthermore, the suppression of BAMBI ameliorated the effect of miR-338-3p inhibition against ox-LDL-induced HUVEC cell injury. In conclusion, our study thus suggests that miR-338-3p promoted ox-LDL-induced HUVEC cell injury by targeting BAMBI and activating the TGF-β/Smad pathway, which may provide a novel and promising therapeutic target for AS.

Keywords: BMP and activin membrane-bound inhibitor (BAMBI); TGF-β/Smad pathway; atherosclerosis (AS); microRNA-338-3p; oxidized low-density lipoprotein (ox-LDL).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Atherosclerosis / metabolism
  • Cell Proliferation
  • Cell Survival / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelium, Vascular* / cytology
  • Endothelium, Vascular* / drug effects
  • Gene Expression Regulation / drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipoproteins, LDL / toxicity*
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Smad Proteins / genetics
  • Smad Proteins / metabolism*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation / drug effects

Substances

  • BAMBI protein, human
  • Lipoproteins, LDL
  • MIRN338 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Smad Proteins
  • Transforming Growth Factor beta
  • oxidized low density lipoprotein