LncRNA TUG1 silencing enhances proliferation and migration of ox-LDL-treated human umbilical vein endothelial cells and promotes atherosclerotic vascular injury repairing via the Runx2/ANPEP axis

Int J Cardiol. 2021 Sep 1:338:204-214. doi: 10.1016/j.ijcard.2021.05.014. Epub 2021 May 8.

Abstract

The role of vascular endothelial cell injury in the course of atherosclerosis (AS) has attracted increasing attention. Long non-coding RNAs (LncRNAs) are demonstrated to be the biomarker for the diagnosis of AS. This study investigated the mechanism of lncRNA taurine upregulated gene 1 (TUG1) in AS. Microarray data of AS obtained from GEO database showed that lncRNA TUG1 was differentially expressed in AS samples. TUG1 expression was upregulated in ox-LDL-treated human umbilical vein endothelial cells (HUVECs). Oxidized low density lipoprotein (ox-LDL)-treated HUVECs were then transfected with sh-TUG1. TUG1 silencing promoted proliferation and migration of ox-LDL-treated HUVECs. TUG1 bound to Runt-related transcription factor 2 (Runx2). Runx2 silencing promoted proliferation and migration of HUVECs. The downstream genes of Runx2 were predicted by hTFtarget database. The binding site of Runx2 and Aminopeptidase N (ANPEP) was determined. Runx2 silencing reversed the repression effect of overexpressing ANPEP on cell proliferation and migration. TUG1 silencing inhibited ANPEP expression via Runx2 to promote HUVEC proliferation and migration. A mouse model of AS was established. The area of atherosclerotic lesions of mouse aorta was detected, and vascular re-endothelialization was evaluated. TUG1 silencing promoted vascular injury repairing and inhibited AS in vivo. In conclusion, TUG1 silencing enhanced proliferation and migration of ox-LDL-treated HUVECs and promoted vascular injury repairing in vivo via the Runx2/ANPEP axis.

Keywords: ANPEP; Atherosclerosis; Endothelial cells; LncRNA TUG1; Proliferation and migration; Runx2.

MeSH terms

  • Animals
  • Atherosclerosis* / genetics
  • CD13 Antigens
  • Cell Proliferation
  • Core Binding Factor Alpha 1 Subunit
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipoproteins, LDL
  • Mice
  • MicroRNAs*
  • RNA, Long Noncoding* / genetics
  • Taurine
  • Vascular System Injuries*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Lipoproteins, LDL
  • MicroRNAs
  • RNA, Long Noncoding
  • Runx2 protein, mouse
  • TUG1 long noncoding RNA, human
  • long non-coding RNA TUG1, mouse
  • oxidized low density lipoprotein
  • Taurine
  • CD13 Antigens