Role of long non-coding RNA-RNCR3 in atherosclerosis-related vascular dysfunction.

K Shan,C Liu,M -D Yao,Yong J,H Yang,X -Q Wang,B Yan,Y -Y Zhang,Q Jiang,J Yao,X -M Li,B Liu,Y -N -Z Wang

doi:10.1038/cddis.2016.145

Abstract

Atherosclerosis is one of the most common vascular disorders. Endothelial cell (EC) dysfunction and vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis. Long non-coding RNAs (lncRNAs) have been implicated in several biological processes and human diseases. Here we show that lncRNA-RNCR3 is expressed in ECs and VSMCs. RNCR3 expression is significantly upregulated in mouse and human aortic atherosclerotic lesions, and cultured ECs and VSMCs upon ox-LDL treatment in vitro. RNCR3 knockdown accelerates the development of atherosclerosis, aggravates hypercholesterolemia and inflammatory factor releases, and decreases EC and VSMC proliferation in vivo. RNCR3 knockdown also reduces the proliferation and migration, and accelerates apoptosis development of EC and VSMC in vitro. RNCR3 acts as a ceRNA, and forms a feedback loop with Kruppel-like factor 2 and miR-185-5p to regulate cell function. This study reveals that RNCR3 has an atheroprotective role in atherosclerosis, and its intervention is a promising strategy for treating atherosclerosis-related vascular dysfunction.

Highlights

Long non-coding RNAs constitute a class of transcripts longer than 200 nucleotides.[8]
We found that viral short hairpin RNA (shRNA) injection did not induce a detectable immune response, as serum levels of IL-6 and monocyte chemoattractant protein 1 (MCP-1) in mice treated with scrambled shRNA or Retinal non-coding RNA3 (RNCR3) shRNA did not differ from that of mice injected with PBS alone
RNCR3 acts as a competing endogenous RNA (ceRNA), and forms a feedback loop with Kruppel-like factor 2 (KLF2) and miR-185-5p to elicit

Summary

Introduction

Long non-coding RNAs (lncRNAs) constitute a class of transcripts longer than 200 nucleotides.[8]. (c–f) Four-week-old male ApoE− / − mice were fed with high-fat diet containing 0.15% cholesterol and 20% fat for 16 weeks. (b) RNCR3 expression was detected in atherosclerotic lesions and non-lesional aortic intimal tissues from human aortas (*Po0.05). They were received a subcutaneous injection of scrambled shRNA (Scr) or RNCR3 shRNA viral vector (R), or PBS. Representative en face Oil red O staining in the aortas of PBS-, scrambled shRNA-, and RNCR3 shRNA-injected mice. Representative oil red O staining of aortic sinus in PBS-, scrambled shRNA-, and RNCR3 shRNA-injected mice.

Methods

Results

Conclusion