Downregulation of microRNA‑106a‑5p alleviates ox‑LDL‑mediated endothelial cell injury by targeting STAT3

Mol Med Rep. 2020 Aug;22(2):783-791. doi: 10.3892/mmr.2020.11147. Epub 2020 May 14.

Abstract

The apoptosis of endothelial cells (ECs) induced by oxidized low‑density lipoprotein (ox‑LDL) is an important contributing factor in the pathogenesis of atherosclerosis. It has been reported that microRNA (miR)‑106a‑5p is overexpressed in atherosclerotic plaques and involved in angiogenesis. However, its role and underlying mechanisms in ox‑LDL induced EC apoptosis remain to be fully understood. In the present study the expression of miR‑106a‑5p in human umbilical vein ECs (HUVECs) stimulated with ox‑LDL was investigated using reverse transcription‑quantitative PCR analysis. Cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Caspase‑3 activity and reactive oxygen species (ROS) levels were determined by commercial kits. The interaction between miR‑106a‑5p and signal transducer and activator of transcription 3 (STAT3) mRNA was examined by luciferase reporter assay. It was found that ox‑LDL treatment significantly increased the levels of miR‑106a‑5p in a dose‑dependent manner in HUVECs. Moreover, these results demonstrated that ox‑LDL treatment inhibited cell viability, promoted cell apoptosis, increased caspase‑3 activity and ROS levels, whereas inhibition of miR‑106a‑5p reversed the effects of ox‑LDL on HUVECs. In addition, it was shown that STAT3 is a direct target of miR‑106a‑5p in HUVECs, and silencing of STAT3 impaired the protective effects of miR‑106a‑5p inhibition on cell apoptosis and oxidative injury induced by ox‑LDL. Collectively, these results indicated that miR‑106a‑5p participated in ox‑LDL‑stimulated apoptosis and oxidative injury in HUVECs by regulating STAT3. Thus, suggesting that miR‑106a‑5p/STAT3 may serve as a novel therapeutic target for atherosclerosis in the future.

Keywords: endothelial cells; apoptosis; microrna-106a-5p; oxidized low-density lipoprotein; atherosclerosis; human umbilical vein endothelial cells; cell viability.

MeSH terms

  • Apoptosis / genetics
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Caspase 3 / metabolism
  • Cell Survival / genetics
  • Cells, Cultured
  • Down-Regulation
  • Gene Knockdown Techniques
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Lipoproteins, LDL / pharmacology*
  • MicroRNAs / drug effects
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Oxidative Stress / drug effects
  • RNA, Small Interfering
  • Reactive Oxygen Species / metabolism
  • STAT3 Transcription Factor / metabolism*

Substances

  • Lipoproteins, LDL
  • MIRN106 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • oxidized low density lipoprotein
  • CASP3 protein, human
  • Caspase 3