MiR-182-5p Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by ox-LDL Through Targeting PAPPA

Int Heart J. 2020 Jul 30;61(4):822-830. doi: 10.1536/ihj.19-708. Epub 2020 Jul 18.

Abstract

This study aims to analyze the expression level and correlation of miR-182-5p and its target gene PAPPA in coronary atherosclerosis (CAD).Real time PCR, ELISA, and Western blotting methods were used to detect the expression levels. Dual-luciferase reporter gene assays were used to analyze the interaction between the 3'-UTR of PAPPA and miR-182-5p.The expression level of miR-182-5p in CAD was significantly lower than that in normal population, while the content of serum PAPPA was significantly increased, and the expression level of miR-182-5p was negatively correlated with the PAPPA content. The expression level of miR-182-5p decreased, while the expression level of PAPPA increased significantly in the ox-LDL treated HA-VSMC cells. Researchers found that PAPPA could promote the activation of IGF signaling pathway in HA-VSMC cells treated by ox-LDL, further activate NF-kB, PI3K/AKT and ERK signaling pathway, and promote cell proliferation. However, miR-182-5p could inhibit the expression of PAPPA, block the activation of IGF signal pathway, and inhibit the proliferation of HA-VSMC cells induced by ox-LDL. miR-182-5p had a targeted action site in the 3'-UTR of PAPPA by bioinformatics prediction. The analysis of luciferase reporter gene further confirmed that miR-182-5p could target the 3'-UTR of PAPPA to inhibit its expression.miR-182-5p demonstrated a protective effect on atherosclerosis and may be a potential therapeutic target for atherosclerosis.

Keywords: Atherosclerosis; RNA interference; Signaling pathway; miRNAs; qRT-PCR.

MeSH terms

  • Cells, Cultured
  • Coronary Artery Disease / blood*
  • Humans
  • MAP Kinase Signaling System
  • MicroRNAs / blood*
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / metabolism*
  • Pregnancy-Associated Plasma Protein-A / metabolism*

Substances

  • MicroRNAs
  • Mirn182 microRNA, human
  • Pregnancy-Associated Plasma Protein-A