Analysis of MCM Proteins’ Role as a Potential Target of Statins in Patients with Acute Type A Aortic Dissection through Bioinformatics

Acute aortic dissection is one of the most severe vascular diseases. The molecular mechanisms of aortic expansion and dissection are unclear. Clinical studies have found that statins play a protective role in aortic dissection development and therapy; however, the mechanism of statins’ effects on the aorta is unknown. The Gene Expression Omnibus (GEO) dataset GSE52093, GSE2450and GSE8686 were analyzed, and genes expressed differentially between aortic dissection samples and normal samples were determined using the Networkanalyst and iDEP tools. Weight gene correlation network analysis (WGCNA), functional annotation, pathway enrichment analysis, and the analysis of the regional variations of genomic features were then performed. We found that the minichromosome maintenance proteins (MCMs), a family of proteins targeted by statins, were upregulated in dissected aortic wall tissues and play a central role in cell-cycle and mitosis regulation in aortic dissection patients. Our results indicate a potential molecular target and mechanism for statins’ effects in patients with acute type A aortic dissection.

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Identification of Molecular Regulatory Features and Markers for Acute Type A Aortic Dissection

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/6697848 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Rui Lian ◽

Guochao Zhang ◽

Shengtao Yan ◽

Lichao Sun ◽

Guoqiang Zhang

Keyword(s):

Aortic Dissection ◽

T Cell Activation ◽

Molecular Mechanisms ◽

Type A ◽

R Package ◽

Acute Type ◽

Ppi Network ◽

Hub Genes ◽

Type A Aortic Dissection ◽

And Control

Background. Acute type A aortic dissection (ATAAD) is one of the most lethal cardiovascular diseases, and its molecular mechanism remains unclear. Methods. Differentially expressed genes (DEGs) between ATAAD and control were detected by limma R package in GSE52093, GSE153434, GSE98770, and GSE84827, respectively. The coexpression network of DEGs was identified by the WGCNA package. Enrichment analysis was performed for module genes that were positively correlated with ATAAD using clusterProfiler R package. In addition, differentially methylated markers between aortic dissection and control were identified by ChAMP package. After comparing with ATAAD-related genes, a protein-protein interaction (PPI) network was established based on the STRING database. The genes with the highest connectivity were identified as hub genes. Finally, differential immune cell infiltration between ATAAD and control was identified by ssGSEA. Results. From GSE52093 and GSE153434, 268 module genes were obtained with consistent direction of differential expression and high correlation with ATAAD. They were significantly enriched in T cell activation, HIF-1 signaling pathway, and cell cycle. In addition, 2060 differentially methylated markers were obtained from GSE84827. Among them, 77 methylation markers were ATAAD-related DEGs. Using the PPI network, we identified MYC, ITGA2, RND3, BCL2, and PHLPP2 as hub genes. Finally, we identified significantly differentially infiltrated immune cells in ATAAD. Conclusion. The hub genes we identified may be regulated by methylation and participate in the development of ATAAD through immune inflammation and oxidative stress response. The findings may provide new insights into the molecular mechanisms and therapeutic targets for ATAAD.

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

10.21203/rs.2.10144/v1 ◽

2019 ◽

Author(s):

maoxun huang ◽

hulin piao ◽

yong wang ◽

weitie wang ◽

bo li ◽

...

Keyword(s):

Aortic Dissection ◽

Molecular Mechanisms ◽

Target Genes ◽

Critical Role ◽

Type A ◽

Integrated Analysis ◽

Acute Type ◽

Type A Aortic Dissection ◽

Cerna Network ◽

Key Genes

Abstract 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

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