| Objective:Aortic dissection(AD)is a rare and fatal disease,particularly Stanford type A,and its genetic basis remains largely unknown.Many studies have shown that long-stranded noncoding RNAs(lncRNAs)play an important role in the development of various diseases.However,the role of lncRNAs in the pathogenesis of AD is unclear and still needs to be further explored.In this study,we used the more representative Stanford type A aortic dissection to elucidate the potential molecular mechanisms of lncRNA regulation in AD based on the lncRNA-associated competitive endogenous RNA(ceRNA)network.Methods:1.Aortic tissue was obtained from five patients with Stanford type A acute aortic dissection and from five patients with ischemic heart disease.2.Microarray data were analyzed using microarray analysis technology to obtain mRNA and lncRNA gene expression profiles from the aorta of 5 Stanford type A acute aortic dissection patients and the aorta of 5 ischemic heart disease patients.3.Differential analysis of mRNA and lncRNA expression data was performed,and differentially expressed mRNAs(differentially expressed genes,DEGs)and differentially expressed lncRNAs(differentially expressed lncRNAs,DELs)were obtained.The aortic dissection mi RNAs expression dataset GSE98770 was obtained from the GEO database,and differentially expressed mi RNAs(differentially expressed mi RNAs,DEMs)were obtained by differential analysis.4.All DEGs were subjected to gene ontology and pathway enrichment analysis using the online bioinformatics database David,and the central genes in aortic dissection pathogenesis were analyzed and obtained by protein-protein interaction(PPI).5.The top ten central genes were selected and the targeting relationships of DELs-DEMs and DEGs-DEMs were predicted by Target Scan and ENCORI database,and then the ceRNA network of aortic dissection was constructed.6.Obtain aortic dissection gene expression profiles from the GEO database and verify the lncRNA-mRNA interactions and expression levels in the ceRNA network by linear regression analysis.Results:Differential expression analysis identified 161 differentially expressed lncRNAs(DELs),87 differentially expressed mi RNAs(DEmi Rs)and 103 differentially expressed mRNAs(DEGs).According to GO and KEGG analysis,GO analysis showed that the down-regulated differential mRNAs were enriched in muscle contraction and energy metabolism in AD and were significant in aortic mesoderm.Up-regulated differential mRNAs were concentrated in cellular autophagy and apoptosis,suggesting that oxidative stress,inflammation and apoptosis may be central to AD.KEGG analysis showed that the up-regulated genes were mainly concentrated in the lysosomal pathway and apoptotic pathway,and the down-regulated genes were mainly concentrated in the Salmonella salmonicida infection pathway.Thus,GO and KEGG analysis revealed the importance of apoptosis,extracellular matrix imbalance,and oxidative stress in aortic vascular smooth muscle during AD.We constructed ceRNA networks for further statistical comparison,including one lncRNA,four mi RNAs and seven mRNAs.linear regression analysis suggested a good positive correlation between lncRNA and partial mRNA expression levels in ceRNAs.We finally identified three lncRNA-mi RNA-mRNA regulatory axes,namely the LOX axis(LINC01355-hsa-mi R-145-5p/ hsa-mi R-186-5p/ hsa-mi R-30a-5p/hsa-mi R-30c-5p-LOOS),the CTSS axis(LINC01355-hsa-mi R-186-5p-CTSS)and VCAN axes(LINC01355-hsa-mi R-186-5p/ hsa-mi R-30a-5p/ hsa-mi R-30c-5p-VCAN).Conclusion:The ceRNA interaction axis was found to be a potential key target for the treatment of AD.Differentially expressed lncRNAs,mi RNAs and mRNAs for AD were screened using bioinformatics tools,and functional and signaling pathway enrichment analyses were performed to finally construct an aortic clamping ceRNA network and validate the expression levels.Among them,LOX axis(LINC01355-hsa-mi R-145-5p/hsa-mi R-186-5p/ hsa-mi R-30a-5p/ hsa-mi R-30c-5p-LOOS),CTSS axis(LINC01355-hsa-mi R-186-5p-CTSS)and VCAN axis(LINC01355-hsa-mi R-186-5p/ hsa-mi R-30a-5p/hsa-mi R-30c-5p-VCAN)may have important roles in aortic dissection.Our findings suggest that lncRNA-related ceRNA networks may provide additional insight into possible pathogenic mechanisms of AD. |
