Comprehensive molecular characterization of circRNA-associated ceRNA network in constrictive pericarditis

Background: Aberrant gene expression occurs in almost all diseases including constrictive pericarditis (CP). However, the dysregulation of genes underlying the CP remains unclear. This study aims to investigate the potential molecular mechanisms underlying CP and screen hub genes critical for the pathogenesis of CP. Methods: Differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs in pericardial tissues were screened using RNA-seq in CP patients and controls. Furthermore, functional annotation analysis and protein-protein interaction (PPI) network were carried out to investigate the potential key pathways and identify hub genes in CP. Subsequently, a ceRNA network was established and the key circRNAs were determined by Gene Set Enrichment Analysis (GSEA). Finally, the corresponding RNA-seq results were confirmed and validated with a quantitative real time-PCR (qRT-PCR). Results: Functional annotation analysis revealed that differentially expressed mRNAs (DEMs) mainly participated in inflammatory response related pathways and the 10 top genes with the highest degree in PPI network were considered as the hub genes. In addition, a total of 377 regulatory relationships among the differentially expressed genes (DEGs) could be constructed, from which a subsequent ceRNA network was also established, while the circRNAs were further validated with qRT-PCR and the key biological pathways were identified using GSEA as well. Conclusions: The genes determined to have altered expression levels in CP may participate in a number of biological signaling processes leading to inflammation and fibrosis frequently encountered in CP, and, therefore, our novel findings may provide an insight into the pathogenesis, molecular biomarkers, and potential therapeutic targets in CP.