Long noncoding RNA CASC2 inhibits ox-LDL-mediated vascular smooth muscle cells proliferation and migration via the regulation of miR-532-3p/PAPD5

Chenjing Wang,Jin Zhao,Xiaokun Wang,Shuangsheng Huang,Xiaodong Nan,Zhong Guo,Shijie Ma,Feng Sun

doi:10.1186/s10020-020-00200-3

Abstract

BackgroundStudies have demonstrated that long noncoding RNAs (lncRNAs) have essential impacts on the development of atherosclerosis (AS). This study aimed to identify the role and functional mechanism of lncRNA CASC2 in the development and migration of vascular smooth muscle cells (VSMCs).MethodThe serum of 40 pairs of AS patients and healthy volunteers were collected and the expression of CASC2 was evaluated. qRT-PCR and western blotting were carried out to examine the expression levels of at mRNA and protein level, repectively. Cell proliferation assay, colony formation assay, transwell migration assay, dual-luciferase reporter assay, and wound healing assay were conducted to evaluate cell proliferation, colony formation, migration, transcription, targeting, and self-restoration.ResultsThe expression levels of CASC2 were decreased, while the expression levels of miR-532-3p were elevated in AS patient samples and VSMCs. Overexpression of CASC2 inhibited the proliferation and migration of VSMCs and enhanced cell apoptosis. CASC2 inhibited the expression of miR-532-3p, and inversely upregulated the expression of PAPD5, which was a target of miR-532-3p. In addition, knockdown of miR-532-3p-mimic and PAPD5 could attenuate the impact of overexpression of CASC2 on proliferation, migration, and apoptosis in ox-LDL-VSMCs.ConclusionCASC2 suppressed cell reproduction and promoted cell apoptosis by regulating the miR-532-3p/PAPD5 axis in ox-LDL-mediated VSMCs. This might be important for AS therapeutics.

Highlights

Studies have demonstrated that long noncoding RNAs have essential impacts on the development of atherosclerosis (AS)
CASC2 inhibited the expression of miR-532-3p, and inversely upregulated the expression of PAPD5, which was a target of miR-532-3p
Knockdown of miR-532-3p-mimic and PAPD5 could attenuate the impact of overexpression of CASC2 on proliferation, migration, and apoptosis in Oxidized low-density lipoprotein (ox-LDL)-vascular smooth muscle cells (VSMCs)

Summary

Introduction

Studies have demonstrated that long noncoding RNAs (lncRNAs) have essential impacts on the development of atherosclerosis (AS). This study aimed to identify the role and functional mechanism of lncRNA CASC2 in the development and migration of vascular smooth muscle cells (VSMCs). The development of atherosclerosis is related with multiple processes, including the production of pro-inflammatory factors (Ross, 1999), dysfunction of vascular smooth muscle cells (VSMCs) (Bennett et al, 2016), and dysregulation of specific RNAs and proteins (Burd et al, 2010). One study demonstrated that lncRNA GAS5 regulated the apoptosis of macrophages and vascular endothelial cells in atherosclerosis (Chen et al, 2017). We aimed to explore the roles of CASC2 in the proliferation of vascular smooth muscle cells and the underlying mechanisms in atherosclerosis

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