Abstract
Hypertrophic cardiomyopathy (HCM), the most common heritable cardiomyopathy, is associated with a high risk of sudden cardiac death. The complexity and behavior of the circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) network in HCM have not been thoroughly elucidated. Plasma circRNA and messenger RNA (mRNA) expression profiles were acquired by using a microarray. Weighted correlation network analysis (WGCNA) and linear models for microarray data (Limma) were used to analyze microarray data. Gene modules, consisting of genes with high correlations, were detected and represented by a designated color. The ceRNA network, including circRNA, microRNA (miRNA), and mRNA, was constructed based on the “ceRNA hypothesis” using an integrated systems biology method. By WGCNA, two modules, namely magenta and red modules, were identified as being positively correlated with HCM. In the combined analysis of WGCNA and Limma, 36 hub circRNAs in the magenta module and 83 hub circRNAs in the red module were significantly upregulated compared with the controls. By coexpression analysis, 270 circRNA–mRNA pairs were identified with a coefficient ≥0.9 and p < 0.05. With Starbase and miRWalk tools, circRNA–miRNA pairs and miRNA–mRNA pairs were predicted. Once these pairs were combined, the ceRNA network with 6 circRNAs, 29 miRNAs, and 6 mRNAs was constructed. Functional analysis demonstrated that these circRNAs in the ceRNA network were associated with calcium-release channel activity and muscle filament sliding. Our study provided a global perspective and systematic analysis of the circRNA-associated ceRNA network in HCM. The identified circRNAs hsa_circ_0043762, hsa_circ_0036248, and hsa_circ_0071269 may be key regulators involved in HCM pathogenesis.
Highlights
Hypertrophic cardiomyopathy (HCM) is widely recognized as an autosomal dominantly inherited cardiac disorder, and its prevalence has increased considerably with the popularization of genomic sequencing (Elliott et al, 2014)
We identified differentially expressed circular RNA (circRNA) using the linear models for microarray data (Limma) package in R (Ritchie et al, 2015)
Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that hsa_circ_0036248 might be associated with the regulation of transient receptor potential (TRP) channels, adrenergic signaling in cardiomyocytes, and calcium signaling pathways. hsa_circ_0071269 may be associated with the regulation of TRP channels and dilated cardiomyopathy
Summary
Hypertrophic cardiomyopathy (HCM) is widely recognized as an autosomal dominantly inherited cardiac disorder, and its prevalence has increased considerably with the popularization of genomic sequencing (Elliott et al, 2014). The discovery of HCM-causing mutations has contributed to a strong improvement in the management of risk for adverse outcomes, such as sudden cardiac death, heart failure, atrial fibrillation, and non-fatal stroke (Olivotto et al, 2008). It is of considerable importance to expand the HCM research focus beyond a single molecular event toward more inclusive models, including transcriptional or epigenetic factors, to explain this disease in its entirety. Several studies have indicated circRNAs with cardiac hypertrophy and fibrosis, both of which are important pathological changes in HCM (Wang et al, 2016; Yousefi and Soltani, 2020). It is hypothesized that circRNAs may play vital roles in the pathogenesis of HCM
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call