Abstract
Hypertrophic cardiomyopathy (HCM) is a complex inherited cardiovascular disease. The present study investigated the long noncoding (lnc)RNA/microRNA (mi)RNA/mRNA expression pattern of patients with HCM and aimed to identify key molecules involved in the development of this condition. An integrated strategy was conducted to identify differentially expressed miRNAs (DEmiRs), differentially expressed lncRNAs (DElncs) and differentially expressed genes (DEGs) based on the GSE36961 (mRNA), GSE36946 (miRNA), GSE68316 (lncRNA/mRNA) and GSE32453 (mRNA) expression profiles downloaded from the Gene Expression Omnibus datasets. Bioinformatics tools were employed to perform function and pathway enrichment analysis, protein-protein interaction, lncRNA-miRNA-mRNA and hub gene networks. Subsequently, DEGs were used as targets to predict drugs. The results indicated that a total of 2,234 DElncs (1,120 upregulated and 1,114 downregulated), 5 DEmiRs (2 upregulated and 3 downregulated) and 42 DEGs (35 upregulated and 7 downregulated) were identified in 4 microarray profiles. Gene ontology analysis revealed that DEGs were mainly involved in actin filament and stress fiber formation and in calcium ion binding, whereas Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the hypoxia inducible factor-1, transforming growth factor-β and tumor necrosis factor signaling pathways as the main pathways involved in these processes. The hub genes were screened using cytoHubba. A total of 1,086 lncRNA-miRNA-mRNA interactions including 67 lncRNAs, 5 miRNAs and 25 mRNAs were mined in the present study based on prediction websites. Drug prediction indicated that the targeted drugs mainly included angiotensin converting enzyme inhibitors or β-blockers. A comprehensive bioinformatics analysis of the molecular regulatory lncRNA-miRNA-mRNA network was performed and potential therapeutic applications of drugs were predicted in HCM patients. The data may unravel the future molecular mechanism of HCM.
Highlights
Hypertrophic cardiomyopathy (HCM) is a heterogeneous monogenic myocardial disorder that is characterized by myocardial hypertrophy, asymmetric hypertrophy of the ventricular septum, decreased ventricular cavity and abnormal hypertrophy of cardiac muscle cells
LncRNA, miRNA and gene microarray expression profiles between HCM and healthy controls were investigated by the Gene Expression Omnibus database (GEO; https://www.ncbi.nlm.nih.gov/geo/) using the keywords ‘hypertrophic cardiomyopathy’ and ‘Long non‐coding RNAs (lncRNAs)’ or ‘miRNA’ or ‘mRNA’
Following prediction and intersection process, 112 non‐redundant lncRNA‐miRNA pairs and 49 miRNA‐mRNA pairs containing 67 lncRNAs, 5 miRNAs and 25 mRNAs were mined in the present study
Summary
Hypertrophic cardiomyopathy (HCM) is a heterogeneous monogenic myocardial disorder that is characterized by myocardial hypertrophy, asymmetric hypertrophy of the ventricular septum, decreased ventricular cavity and abnormal hypertrophy of cardiac muscle cells. With the development of high‐throughput gene expression profiling technology, microarray analysis has been widely used in the early diagnosis, treatment and prognosis of several diseases. MicroRNAs (miRNAs) are a novel class of small non‐coding RNAs, which can negatively regulate gene expression at the post‐transcriptional level by directly binding to mRNAs [5]. Long non‐coding RNAs (lncRNAs) and circular RNAs contain miRNA response elements, acting as competitors of endogenous RNAs [6]. These molecules have emerged as essential regulatory molecules in various biological processes. In 2014, Song et al [7] performed a miRNA microarray analysis on heart tissues from 7 HCM patients and 5 healthy subjects and found that miR‐451 was the main miRNA that was downregulated in the HCM subjects.
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