circRNA/lncRNA-miRNA-mRNA Network in Oxidized, Low-Density, Lipoprotein-Induced Foam Cells

Abstract

Although long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been suggested to play important roles in the pathogenesis of diseases, atherosclerosis-related lncRNAs and circRNAs remain rarely reported. This study aimed to explore the underlying molecular mechanisms of atherosclerosis based on the competing endogenous RNA (ceRNA) regulatory hypothesis of lncRNAs and circRNAs. The expression profiles of circRNAs, lncRNAs, and mRNAs in human THP-1 macrophages treated with oxidized low-density lipoprotein (an <i>in vitro</i> atherosclerosis model), or not, were obtained from the Gene Expression Omnibus database under accession numbers GSE107522, GSE54666, and GSE54039, respectively. The present study identified 29 differentially expressed circRNAs in GSE107522, 544 differentially expressed genes (DEGs) in GSE54666, and 502 DEGs and 231 differentially expressed lncRNAs in GSE54039 datasets by using the Linear Models for Microarray Data method. Eight DEGs were found to be shared and expressed with the consistent trend in GSE54666 and GSE54039 datasets. Two of them (<i>ASPH</i>, aspartate beta-hydroxylase; and <i>PDE3B</i>, phosphodiesterase 3B) were suggested to be crucial based on functional enrichment, protein-protein interaction, and ceRNA network analyses. <i>ASPH</i>, through interaction with <i>CACNA2D4</i> (calcium voltage-gated channel auxiliary subunit alpha2delta 4), may be associated with atherosclerosis by regulating the cellular response to calcium ion; and <i>PDE3B</i> may exert roles in negative regulation of angiogenesis through cross talk with <i>ELMO1</i> (engulfment and cell motility 1). Furthermore, the expression of <i>ASPH</i> and <i>PDE3B</i> may be regulated by hsa_circ_0028198/hsa_circ_0092317/XIST-miR-543; <i>PDE3B</i> expression may be also modulated by hsa_circ_0092317/hsa_circ_0003546/H19/XIST-miR-326. In conclusion, our identified ceRNA interaction axes may possibly be important targets for treatment of atherosclerosis.