Construction of a circRNA-Mediated ceRNA Network Reveals Novel Biomarkers for Aortic Dissection.

Abstract

BackgroundAortic dissection (AD) is a rare and lethal disorder with its genetic basis remains largely unknown. Many studies have confirmed that circRNAs play important roles in various physiological and pathological processes. However, the roles of circRNAs in AD are still unclear and need further investigation. The present study aimed to elucidate the underlying molecular mechanisms of circRNAs regulation in AD based on the circRNA-associated competing endogenous RNA (ceRNA) network.MethodsExpression profiles of circRNAs (GSE97745), miRNAs (GSE92427), and mRNAs (GSE52093) were downloaded from Gene Expression Omnibus (GEO) databases, and the differentially expressed RNAs (DERNAs) were subsequently identified by bioinformatics analysis. CircRNA–miRNA–mRNA ceRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict the potential functions of circRNA-associated ceRNA network. RNA was isolated from human arterial blood samples after which qRT-PCR was performed to confirm the DERNAs.ResultsWe identified 14 (5 up-regulated and 9 down-regulated) differentially expressed circRNAs (DEcircRNAs), 17 (8 up-regulated and 9 down-regulated) differentially expressed miRNAs (DEmiRNAs) and 527 (297 up-regulated and 230 down-regulated) differentially expressed mRNAs (DEmRNAs) (adjusted P-value <0.05 and | log2FC | > 1.0). KEGG pathway analysis indicated that DEmRNAs were related to focal adhesion and extracellular matrix receptor interaction signaling pathways. Simultaneously, the present study constructed a ceRNA network based on 1 circRNAs (hsa_circRNA_082317), 1 miRNAs (hsa-miR-149-3p) and 10 mRNAs (MLEC, ENTPD7, SLC16A3, SLC7A8, TBC1D16, PAQR4, MAPK13, PIK3R2, ITGA5, SERPINA1). qRT-PCR demonstrated that hsa_circRNA_082317 and ITGA5 were significantly up-regulated, and hsa-miR-149-3p was dramatically down-regulated in AD (n = 3).ConclusionThis is the first study to demonstrate the circRNA-associated ceRNA network is altered in AD, implying that circRNAs may play important roles in regulating the onset and progression and thus may serve as potential biomarkers for the diagnosis and treatment of AD.