Identifying Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease

Abstract

Background: Accumulating evidence has indicated that the importance of noncoding RNAs and exosomes in coronary heart disease (CHD). However, the exosomal-associated competing endogenous RNA (ceRNA)-mediated regulatory mechanism in CHD is still unknown. The present study aimed to explore exosomal-associated ceRNA network in CHD.Methods: The dataset, including 6 CHD patients and 32 normal controls, were downloaded from the ExoRBase database. Differentially expressed mRNAs (DEMs), lncRNAs (DELs) and circRNAs (DECs) in the serum exosomes between CHD and normal controls were screened. MicroRNAs (miRNAs) targeting DEMs were predicted by Targetscan and miRanda, miRNAs targeting DELs and DECs were predicted with miRcode and starBase, respectively. The biological functions and related signal pathways of DEMs were analyzed using David and KOBAS database. Subsequently, the protein-protein interaction (PPI) network was established to screen out hub genes, enrichment analyses of hub genes were performed and the ceRNA network (lncRNA/circRNA-miRNA-mRNA) was constructed to elucidate ceRNA axes in CHD.Results: A total of 312 DEMs, 43 DELs and 85 DECs were identified between CHD patients and normal controls. Functional enrichment analysis showed that DEMs were significantly enriched in “chromatin silencing at rDNA”, “telomere organization”, “negative regulation of gene expression, epigenetic”. The PPI network analysis showed that 25 hub DEMs were closely related to CHD, of which, ubiquitin C (UBC) was the most important. The biological function of hub genes showed that they were mainly enriched in “cellular protein metabolic process”. The exosomal-associated ceRNA regulatory network incorporated 48 DEMs, 72 predicted miRNAs, 10 DELs and 15 DECs. LncRNA/circRNA-miRNA-mRNA interaction axes (RPL7AP11/hsa-miR-17-5p/UBC, RPL7AP11/hsa-miR-20b-5p/UBC) were obtained from the network. Conclusions: Our findings have provided a novel perspective on the potential roles of exosomal-associated ceRNA network regulating the pathogenesis of CHD.