Knockdown of long noncoding RNA XIST alleviates oxidative low-density lipoprotein-mediated endothelial cells injury through modulation of miR-320/NOD2 axis

Biochem Biophys Res Commun. 2018 Sep 5;503(2):586-592. doi: 10.1016/j.bbrc.2018.06.042. Epub 2018 Jun 14.

Abstract

Atherosclerosis remains to be one of the most common vascular disorders resulting in morbidity and mortality in the world. Recent studies suggested that endothelial cells (ECs) injury caused by oxidative low-density lipoprotein (ox-LDL) is an early marker for atherosclerosis. Nevertheless, the mechanisms of ox-LDL-induced ECs injury are complicated and largely unknown. Here, we found lncRNA XIST (X-inactive specific transcript) was upregulated in human umbilical vein endothelial cells (HUVECs) stimulated by ox-LDL. Knockdown of XIST boosted the cell viability and suppressed cell apoptosis under ox-LDL stimuli. Further experiments identified XIST regulated the expression of Nucleotide-Binding Oligomerization Domain 2 (NOD2) by sponging miR-320. XIST silencing exerted a protective effect on ox-LDL-induced HUVECs injury via miR-320/NOD2 regulatory network. Our data provide insight into the role of the lncRNA XIST in ox-LDL mediated ECs injury, which can aid in developing new therapeutic strategies for the treatment of atherosclerosis.

Keywords: Atherosclerosis; Endothelial dysfunction; Nucleotide-binding oligomerization domain 2; Oxidative low-density lipoprotein; lncRNA XIST.

MeSH terms

  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Endothelial Cells / metabolism*
  • Gene Expression Regulation*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipoproteins, LDL / metabolism*
  • MicroRNAs / genetics*
  • Nod2 Signaling Adaptor Protein / genetics*
  • RNA Interference
  • RNA, Long Noncoding / genetics*

Substances

  • Lipoproteins, LDL
  • MIRN320 microRNA, human
  • MicroRNAs
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • RNA, Long Noncoding
  • XIST non-coding RNA
  • oxidized low density lipoprotein