CTBP1-AS2 inhibits proliferation and induces autophagy in ox-LDL-stimulated vascular smooth muscle cells by regulating miR-195-5p/ATG14

Abstract

Atherosclerosis (AS) is a chronic progressive disease caused by injury and functional changes in vascular smooth muscle cells (VSMcs). Long non-coding RNAs (lncRNAs) are pivotal regulators in AS development. The present study aimed to explore the roles and molecular mechanisms of lncRNA CTBP1-AS2 in AS progression. A dual-luciferase reporter assay confirmed that miR-195-5p is a downstream target miRNA of lncRNA CTBP1-AS2 and miR-195-5p was increased in AS. The expression levels of miR-195-5p and CTBP1-AS2 in the serums of patients with AS and human aorta vascular smooth muscle cells was increased or decreased, respectively, following treatment with oxidized low-density lipoprotein (ox-LDL). Functional experiments showed that the overexpression of lncRNA CTBP1-AS2 inhibited the proliferation of HA-VSMCs and promoted their autophagy following ox-LdL treatment. This effect could be reversed by treatment with ROC-325, the inhibitor of autophagy, or miR-195-5p mimics. Autophagy related 14 (ATG14) was identified to be a target of miR-195-5p, and lncRNA CTBP1-AS2 promoted ATG14 expression by serving as a competing endogenous RNA of miR-195-5p. The present study revealed that lncRNA CTBP1-AS2 may serve a role in AS by inhibiting the proliferation and promoting the autophagy of VSMCs through ATG14 modulation via miR-195-5p. These data may provide a novel therapeutic target for AS.