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The aim of this study was to explore the pivotal genes or lncRNAs involved in the progression of atrial fibrillation (AF) -valvular heart disease (VHD). The mRNA profiling GSE113013 was obtained from the Gene Expression Omnibus database. The identification of differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) was performed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out for DEGs. Then, the construction of the protein-protein interaction (PPI) network was conducted. An lncRNA-miRNA-target ceRNA network was constructed after obtaining microRNAs (miRNA) related to DElncRNAs. Ultimately, key disease-related genes were screened. A total of 399 DEGs and 145 DElncRNAs were obtained. There were 283 nodes and 588 interaction pairs in the PPI network, and synaptosome-associated protein 25 (SNAP25) had higher degrees (degree = 22) in the PPI network. There were 65 interaction pairs in the ceRNA network. Here, Baculoviral IAP Repeat Containing 5 (BIRC5) was regulated by hsa-miR-1285-3p, which was regulated by lncRNA NPHP3-AS1. Gap Junction Protein Alpha 5 (GAJ5) was regulated by hsa-miR-4505, hsa-miR-1972, and hsa-miR-1199-5p. In particular, GAJ5 was enriched in the function of ion transmembrane transport regulation, whereas BIRC5 was enriched in the function of apoptosis-multiple species pathway. Similarly, Potassium Inwardly Rectifying Channel Subfamily J Member 6 (KCNJ6) was enriched in the function of an ion channel complex. VENN analysis identified BIRC5 and GJA5 as key AF-related genes. KCNJ6, SNAP25, GJA5, BIRC5, hsa-miR-1285-3p, and lncRNA NPHP3-AS1 were likely to be associated with AF-VHD development.


Zhiwei Zhao, Guiqing Liu, Haiyang Zhang, Peng Ruan, Jianjun Ge, Qiang Liu. BIRC5, GAJ5, and lncRNA NPHP3-AS1 Are Correlated with the Development of Atrial Fibrillation-Valvular Heart Disease. International heart journal. 2021;62(1):153-161

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PMID: 33518654

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