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Analyzing the interactions of circRNAs, miRNAs, and mRNAs to predict ceRNA networks in human acute type A aortic dissection


 Background: Acute type A aortic dissection(ATAAD) is a life-threatening vascular disease. However, its underlying mechanism is still not well understood. Here, circular RNAs(circRNAs) were shown to function as competitive endogenous RNAs (ceRNAs) to regulate the effect of microRNAs(miRNAs) on their target genes may play a critical role in ATAAD. However, comprehensive identification and integrated analysis of the circRNA-miRNA-mRNA network in ATAAD have not been performed.
Results: The gene expression profile of circRNAs, miRNAs, and mRNAs was performed between 6 ATAAD patients and 6 age-matched normal ascending aortic wall tissues patients were analyzed using the Arraystar human RNAs microarray. We identified that the expression of 12576 circRNAs,1603 miRNAs, and 14596 mRNAs were found to be differentially expressed(DE). Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses(KEGG) were performed on these DE mRNAs and miRNA-mediated target genes of circRNAs. Furthermore, we used a multi-step computational framework and several bioinformatics methods to construct a ceRNA network containing circRNAs, miRNAs, and mRNAs based on co-expression analysis between the DE genes. The constructed ceRNA regulatory network containing 25 circRNAs, 17 miRNAs and 72 mRNAs. In the whole ceRNA network. We identified that plenty of key genes, such as hsa_circRNA_404522, hsa_circRNA_0022920, hsa_circ_0075881, hsa-miRNA1285-3p, hsa-miRNA-1285-3p, hsa-miRNA-637, hsa-miRNA-650, TINAGL1, JPH4, PLXNA2, TGFBR1, and THSD4. Furthermore, we also integrated the circRNA-miRNA-mRNA regulatory modules of the key genes.
Conclusions: This study found a profile of dysregulated circRNAs, miRNA and mRNAs, and competitive circRNA-miRNA–mRNA regulatory networks were comprehensively integrated and predicted to be involved in ATAAD by GO and KEGG pathway analysis. It might be prospective clinical markers associated with ATAAD, and it is worthwhile to perform further studies to reveal the underlying link between these key genes and the molecular mechanisms of AD.

Keywords：aortic dissection; circRNAs; miRNAs; mRNAs; ceRNA