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Global analysis of circRNA-associated ceRNA network for investigating underlying pathogenesis of constrictive pericarditis (RNA-Seq)

ABSTRACT: Purpose:The purpose of this study is to investigate the potential mechanisms that triggering the onset of constrictive pericarditis and to screen hub genes that exert impact on pathogenesis of patients with constrictive pericarditis. Methods: We screened differentially expressed genes with the data obtained from RNA-seq on CP samples and matched normal samples. Functional annotation analysis and protein-protein interaction (PPI) network were performed to investigate the potential key pathways and genes that play significant roles in CP. Furthermore, the ceRNA network was established and the Gene Set Enrichment Analysis (GSEA) was executed to dig key circRNAs. Results: Following the identification of differentially expressed genes, functional annotation analysis was conducted, suggesting that differentially expressed mRNAs (DEMs) were mainly involved in inflammatory response related pathways. The top 11 genes with the highest degree were extracted from PPI network. A total of 377 predicted regulatory relationships among the differentially expressed genes were found and the ceRNA network was established. Finally, GSEA was conducted on the circRNAs and the key biological pathways were identified. Conclusion: Our study is the pioneering research to analyze the pathogenesis of CP with integrated informatics and we have identified several hub genes, which reveals that the generation of CP is closely related to inflammation and fibrosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122903 | GEO | 2020/05/19

REPOSITORIES: GEO

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Project description:Background: There is growing evidence that circular RNAs (circRNAs) play an important role in a variety of diseases, including erectile dysfunction (ED). Nevertheless, the role of circRNAs in cavernous nerve-damaging ED (CNI-ED) is unknown. Here, we aimed to discover new circRNAs, investigate their potential role in the pathogenesis of CNI-ED, and construct a circRNA-miRNA-mRNA network. Methods: Twelve male Sprague Dawley rats were randomly divided into bilateral cavernous nerve crush (BCNC) and control groups. Four weeks after surgery, the spongy smooth muscle tissue of the rat penis was sequenced using high-throughput full transcriptome sequencing. We analyzed the expression profiles of circRNAs, miRNAs, and mRNAs in the two groups. Twenty circRNAs with significantly different expressions were selected for real-time polymerase chain reaction (RT-qPCR). The circRNA-miRNA-mRNA network was established using Cytoscape. Gene ontology (GO)-term and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the edgeR package. Results: RNA transcriptome sequencing showed that 4,587 circRNAs, 762 miRNAs, and 21,661 mRNAs were dysregulated in the BCNC group. The top 20 differentially expressed circRNAs were further verified via RT-qPCR. The ceRNA network contained 23 circRNA-miRNA pairs and 227 miRNA-mRNA pairs, including ten circRNAs, six miRNAs, and 227 mRNAs. GO analysis suggested that these ten circRNAs could regulate various processes, such as oxidation-reduction processes, lipid metabolic processes, apoptotic processes, and proteolysis. Furthermore, KEGG analysis of mRNAs in the ceRNA network showed that they were involved in energy metabolism and communication between cells. A protein‐protein interaction network was constructed with the 227 mRNAs, and five hub genes (Ccna2, Cxcl10, Pld1, Mapk11, and Mboat2) were identified. In addition, Using circRNADb, we found 12 circRNAs with protein-coding potential, three of which were highly conserved in humans and rats. Our study revealed a potential link between circRNAs, miRNAs, and mRNAs in CNI-ED, suggesting that circRNAs may contribute to the occurrence of ED by regulating the cellular energy metabolism in CNI-ED.

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Global analysis of circRNA-associated ceRNA network for investigating underlying pathogenesis of constrictive pericarditis (RNA-Seq)

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