CircRNA/lncRNA-miRNA-mRNA network in the blood exosomes of patients with atherosclerosis

Abstract

Background: Atherosclerosis (AS) is a systemic, chronic and multifocal disease and is the primary pathological basis of cardiovascular diseases, such as coronary heart disease (CHD) and peripheral arterial disease (PAD). Our study attempted to identify aberrant exosome-derived circRNAs in AS and determine their potential clinical value. Methods: The expression of mRNA, circRNA and lncRNA in the blood exosomes of CHD patients and healthy controls was obtained from the exoRBase database. The corresponding miRNAs of mRNA, circRNA and lncRNA were predicted via ENCORI and the miRcode database. The circRNA/lncRNA-miRNA-mRNA interaction network was established based on a competitive endogenous RNA regulatory mechanism. Aberrant circRNAs in the aforementioned network were validated in patients with PAD by real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Results: Based on the cutoff criteria of P<0.05, we identified 85 differentially expressed circRNAs (4 up- and 81 downregulated), 43 differentially expressed lncRNAs (24 up- and 19 downregulated) and 312 differentially expressed genes (55 up- and 257 downregulated). Gene Ontology (GO) analysis revealed that the biological process (BP) terms of the DEGs were significantly enriched in the positive regulation of phosphoprotein phosphatase activity and the positive regulation of protein dephosphorylation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis demonstrated that DEGs were closely related to the glucagon signaling pathway and estrogen signaling pathway. The relative expression level of hsa_circ_0001360 was significantly downregulated in blood exosomes from patients with PAD, exhibiting an area under the curve of 0.92 (P=0.0283). Conclusion: The circRNA/lncRNA-miRNA-mRNA interaction network might help to elucidate the pathogenesis of AS. Hsa_circ_0001360 was significantly downregulated in blood exosomes in patients with PAD, and this RNA might represent an important diagnostic biomarker of AS.