Construction and Analysis of the lncRNA-miRNA-mRNA Network Based on Competing Endogenous RNA in Atrial Fibrillation

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Abstract
Background: Accumulated studies have revealed that long non-coding RNAs (lncRNAs) play critical roles in human diseases by acting as competing endogenous RNAs (ceRNAs). However, functional roles and regulatory mechanisms of lncRNA-mediated ceRNA in atrial fibrillation (AF) remain unknown. In the present study, we aimed to construct the lncRNA-miRNA-mRNA network based on ceRNA theory in AF by using bioinformatic analyses of public datasets.Methods: Microarray data sets of GSE115574 and GSE79768 from the Gene Expression Omnibus database were downloaded. Twenty-one AF right atrial appendage (RAA) samples and 22 sinus rhythm (SR) subjects RAA samples were selected for subsequent analyses. After merging all microarray data and adjusting for batch effect, differentially expressed genes were identified. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out. A ceRNA network was constructed.Result: A total of 8 lncRNAs and 43 mRNAs were significantly differentially expressed with fold change >1.5 (p < 0.05) in RAA samples of AF patients when compared with SR. GO and KEGG pathway analysis showed that cardiac muscle contraction pathway were involved in AF development. The ceRNA was predicted by co-expressing LOC101928304/ LRRC2 from the constructional network analysis, which was competitively combined with miR-490-3p. The expression of LOC101928304 and LRRC were up-regulated in myocardial tissue of patients with AF, while miR-490-3p was down-regulated.Conclusion: We constructed the LOC101928304/miR-490-3p/LRRC2 network based on ceRNA theory in AF in the bioinformatic analyses of public datasets. The ceRNA network found from this study may help improve our understanding of lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of AF.

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