Abstract
Background. Dilated cardiomyopathy (DCM) is a cardiovascular disease of unknown etiology with progressive aggravation. More and more studies have shown that long noncoding RNAs (lncRNAs) play an essential role in dilated cardiomyopathy formation and development. The mechanism of action of competitive endogenous RNA (ceRNA) networks formed based on the principle that lncRNAs affect mRNAs’ expression level by competitively binding microRNAs (miRNAs) in dilated cardiomyopathy has rarely been reported. Objective. This study is aimed at constructing a lncRNA-miRNA-mRNA ceRNA network by bioinformatics analysis methods, discovering, and validating potential biomarkers of DCM in the ceRNA network and determining possible therapeutic targets from them for drug prediction. Methods. A lncRNA dataset and a mRNA microarray dataset were downloaded from the Gene Expression Omnibus Database (GEO). Gene expression was compared between blood samples from patients with dilated cardiomyopathy and blood samples from normal subjects to identify differential expression of lncRNAs and mRNAs. The lncRNA-miRNA-mRNA network was constructed using bioinformatics tools, and functional and pathway enrichment analysis and protein-protein interactions were performed. The mRNAs in the network and the proteins they encode are then used as targets for predicting drugs. Besides, the expression of lncRNAs in the ceRNA network was validated by real-time quantitative PCR (qRT-PCR) experiments in vitro. Results. The differentially expressed lncRNA-miRNA-mRNA ceRNA network in dilated cardiomyopathy was successfully established. Two differentially overexpressed key lncRNAs were found from the network: AC093817 and AC091062, and qRT-PCR experiments further validated the overexpression of AC093817 and AC091062. The mRNAs in the network and the proteins encoded by the mRNAs were used for drug prediction to get related drugs. Conclusion. This study supports a possible mechanism and drug development of dilated cardiomyopathy, AC093817 and AC091062 being potential biomarkers of dilated cardiomyopathy.
Highlights
Dilated cardiomyopathy is defined as left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal load or coronary artery disease sufficient to cause global systolic function impairment [1]
The early symptoms of dilated cardiomyopathy are not obvious, and many patients have progressed to the terminal stage when they are diagnosed with the disease, which can lead to heart failure or even death [3]
The aim of this study was to identify differentially expressed long noncoding RNAs (lncRNAs) and mRNAs using the limma package in R software. miRNAs were predicted using the miRcode database by differentially expressed lncRNAs, mRNAs were predicted by the combination of Targetscan, miRTarBase, and miRDB databases, and differentially expressed mRNAs and predicted mRNAs were intersected to construct a lncRNAmiRNA-mRNA competitive endogenous RNA (ceRNA) network by Cytoscape software. mRNAs in the network were subjected to GO enrichment analysis, KEGG enrichment analysis, and construction of proteinprotein interaction network
Summary
Dilated cardiomyopathy is defined as left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal load (hypertension, valvular disease) or coronary artery disease sufficient to cause global systolic function impairment [1]. More and more studies have shown that long noncoding RNAs (lncRNAs) play an essential role in dilated cardiomyopathy formation and development. This study is aimed at constructing a lncRNA-miRNA-mRNA ceRNA network by bioinformatics analysis methods, discovering, and validating potential biomarkers of DCM in the ceRNA network and determining possible therapeutic targets from them for drug prediction. Gene expression was compared between blood samples from patients with dilated cardiomyopathy and blood samples from normal subjects to identify differential expression of lncRNAs and mRNAs. The lncRNA-miRNA-mRNA network was constructed using bioinformatics tools, and functional and pathway enrichment analysis and protein-protein interactions were performed. The differentially expressed lncRNA-miRNAmRNA ceRNA network in dilated cardiomyopathy was successfully established. This study supports a possible mechanism and drug development of dilated cardiomyopathy, AC093817 and AC091062 being potential biomarkers of dilated cardiomyopathy
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