Long Noncoding RNA HOXC-AS1 Suppresses Ox-LDL-Induced Cholesterol Accumulation Through Promoting HOXC6 Expression in THP-1 Macrophages

Abstract

Atherosclerosis is a common pathological basis of cardiovascular disease, which remains the leading cause of mortality. Long noncoding RNAs (lncRNAs) are newly studied non-protein-coding RNAs involved in gene regulation, but how lncRNAs exert regulatory effect on atherosclerosis remains unclear. In this study, we found that lncRNA HOXC cluster antisense RNA 1 (HOXC-AS1) and homeobox C6 (HOXC6) were downregulated in carotid atherosclerosis by performing microarray analysis. The results were verified in atherosclerotic plaques and normal arterial intima tissues by quantitative reverse transcription PCR and western blot analysis. Lentivirus-mediated overexpression of HOXC-AS1 induced HOXC6 expression at mRNA and protein levels in THP-1 macrophages. Besides, oxidized low-density lipoprotein (Ox-LDL) decreased expression of HOXC-AS1 and HOXC6 in a time-dependent manner. Induction of cholesterol accumulation by Ox-LDL could be partly suppressed by overexpression of HOXC-AS1.

KCNQ1OT1, HIF1A‐AS2 and APOA1‐AS are promising novel biomarkers for diagnosis of coronary artery disease

“…Our initial quantitative real‐time RT‐PCR (qPCR) analysis included atherosclerosis‐ or cardiac‐related lncRNAs: lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), hypoxia‐inducible factor 1 alpha‐antisense RNA2 (HIF1A‐AS2) and apolipoprotein A‐1 antisense RNA (APOA1‐AS) . As illustrated, the three lncRNAs were significantly higher in PBMC samples from CAD patients than in those from healthy subjects.…”

LncRNA ENST00113 promotes proliferation, survival, and migration by activating PI3K/Akt/mTOR signaling pathway in atherosclerosis

“…Gene chips and other high-throughput sequencing tools have received increasing attention, especially in cancer research. Huang [ 15 ] found that lncRNA HOXC-AS1 and HOXC6 were down-regulated in carotid atherosclerosis by microarray analysis. Singh [ 22 ] assessed the expression profiles of lncRNAs and protein-coding mRNAs in endothelial cells 24 hours after stimulation of oxidized low-density lipoprotein (100 μg/mL) with Arraystar human lncRNA expression microarray V3.0.…”

“…This indicates that lncRNA HOXC-AS1 can be perceived as a method of therapy for atherosclerosis. [ 15 ] Previous studies have shown that lncRNAs can be important regulators of cell apoptosis, proliferation, and differentiation of ECs and VSMCs. [ 16 – 18 ] Although previous studies involved some noncoding RNAs, the exact mechanisms of atherosclerosis and lncRNAs were largely unknown until now.…”

Angio-LncRs: LncRNAs that regulate angiogenesis and vascular disease

“…One of the upregulated lncRNAs, lincRNA-DYNLRB2-2, was shown to promote ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux from THP-1 macrophage-derived foam cells, and inhibit the inflammatory response ( Figure 4 C ) 101 . LncRNA HOXC cluster antisense RNA 1 (HOXC-AS1) and its nearby gene HOXC6 were downregulated by Ox-LDL in THP-1 cells, and reduced in renal arterial intima tissues and advanced atherosclerotic plaques in patients 102 . Lentivirus-mediated overexpression of HOXC-AS1 induced HOXC6 expression, and suppressed the induction of cholesterol accumulation by Ox-LDL, suggesting a protective role for HOXC-AS1 in atherosclerosis ( Figure 4 D ).…”