Abstract
BACKGROUND: Atherosclerosis (AS) is a chronic inflammatory disease that plays a major role in cardiovascular disease. Circular RNAs (circRNAs) are related to the pathogenesis of AS, including the inflammatory response. This study aimed to explore the underlying mechanisms of circRNAs and how they regulate the inflammatory response in AS. METHODS: Analyzed the expression profile of circRNAs in three oxidized low-density lipoprotein (oxLDL) treated macrophage samples and three macrophage control samples using bioinformatics methods. Expression and biological function of circRNA were verified in oxLDL-induced THP-1 macrophages. MiRNAs and target genes of circRNA were predicted by functional enrichment analysis. Expression and function of circRNA target miRNAs were explored in oxLDL-induced THP-1 macrophages. Finally, we predicted and analyzed the function of circRNAs-miRNAs target genes in AS. RESULTS: We identified nine upregulated circRNAs and found that circ_0050486 was significantly upregulated in a THP-1 + PMA + oxLDL group compared with a THP-1 + PMA group. Additionally, circ_0050486 knockdown markedly inhibited IL-6 and TNF-α concentrations and the cell death rates in oxLDL-induced THP-1 macrophages. Furthermore, circ_0050486 targeted and inhibited miR-145 and miR-1270. Upregulated miR-1270 markedly inhibited IL-6 and TNF-α levels and the cell death rates in oxLDL-induced THP-1 macrophages. Finally, the target genes of miR-1270 and miR-145 were predicted by the miRDB, miRWalk, and Targetscan databases, and a functional analysis network of the target genes was constructed by Cytoscape GlueGO, including the regulation of the immune response and monocyte chemotaxis. The common target genes of miR-145 and miR-1270 were established by Cytoscape and included NF1A, among others. CONCLUSIONS: Our study suggested that circ_0050486 knockdown inhibited inflammation and apoptosis by targeting miR-1270 in oxLDL-induced THP-1 macrophages. This finding may provide a potential therapeutic target for atherosclerosis.