Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7214901 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Chen Yixin Y Sun Feifei F Zhang Yong Y Song Guang G Qiao Wei W Zhou Ke K Ren Sihua S Zhao Qian Q Ren Weidong W

Annals of translational medicine 20200401 8

<h4>Background</h4>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.<h4>Methods</h4>Differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs in pericardial tissues were screened using RNA-seq in CP patients and controls. Furthermore, functi ...[more]

PMID: 32411772

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Project description:RNAs are closely associated with human diseases; however, immune-related genes (IRGs) and their potential regulatory networks in relation to spinal cord injury (SCI) are still poorly understood. Here, we investigated the key IRGs as well as the competing endogenous RNA (ceRNA) mechanisms that are associated with SCI pathogenesis based on microarray datasets and the use of a rat SCI model. Specifically, four independent SCI microarray datasets from Gene Expression Omnibus (GEO) database were analyzed and, thereafter, differentially expressed IRGs were annotated via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Furthermore, based on the GEO datasets, differentially expressed RNAs (DERNAs), including DEcircRNAs, DEmiRNAs, and DEmRNAs were identified and interactions between them were also predicted using online databases, and to construct a circular RNA (circRNA) mediated ceRNA network, candidate RNAs were also identified. Furthermore, the support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) methods were used for the identification of critical DERNAs, while differential gene expression was validated using the GSE20907 dataset. Our results were as follows. In the SCI microarray datasets, 32, 58, and 74 DEIRGs, DEcircRNAs, and DEmiRNAs were identified, respectively. In addition, GO and KEGG analyses showed that the DEIRGs were primarily enriched in neutrophil-mediated immunity and nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor-1 (HIF-1) signaling pathways, and based on LASSO and SVM screening, PLXNB2 was identified as a DEIRG, while hsa_circ_0026646 was identified as the key circRNA, showing a higher SCI expression. Furthermore, our results proved that PLXNB2 and hsa_circ_0026646 were upregulated in SCI, whereas miR-331-3p was downregulated, and, interestingly, similar expression profiles were confirmed using the rat SCI model. Furthermore, fluorescent reporter assay indicated that both hsa_circ_0026646 and PLXNB2 have miR-331-3p target sites, and the ceRNA hypothesis suggested the dysregulation of hsa_circ_0026646, miR-331-3p, and PLXNB2 in SCI. Thus, our results suggested that in SCI pathogenesis, hsa_circ_0026646 correlates with PLXNB2 by targeting miR-331-3p.

Dataset Information

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

Publications

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

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