Analysis of changes in circular RNA expression and construction of ceRNA networks in human dilated cardiomyopathy

Abstract

Dilated cardiomyopathy (DCM) is a severe life‐threatening disease worldwide, and the underlying mechanisms remain unclear. Circular RNAs (circRNAs) have been reported to play important roles in various cardiovascular diseases and can function as competitive endogenous RNAs (ceRNAs). However, their role in human DCM has not been fully elucidated. In the present study, heart samples from DCM patients and healthy controls were used to identify circRNAs by RNA sequencing. Real‐time quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) was conducted to validate differentially expressed circRNAs and mRNAs. A total of 9585 circRNAs and 22050 mRNAs were detected in the two groups. Overall, 213 circRNAs and 617 mRNAs were significantly up‐regulated in the DCM group compared with the control group. Similarly, 85 circRNAs and 1125 mRNAs were significantly down‐regulated. According to the ceRNA theory, circRNAs can indirectly interact with mRNAs by directly binding to microRNAs (miRNAs), and circRNAs and mRNAs should be concurrently either up‐regulated or down‐regulated. Based on this theory, we constructed two circRNA‐miRNA‐mRNA networks by using the RNA sequencing data and prediction by proprietary software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to probe the potential functions of differentially expressed circRNAs. In conclusion, this study revealed that the expression of cardiac circRNAs was altered in human DCM and explored the potential functions of circRNAs by constructing ceRNA networks. These findings provide a foundation for future studies of circRNAs in DCM.

Circulating circRNA as biomarkers for dilated cardiomyopathy etiology

“…Recent studies have described several circRNA expression profiles in the DCM population compared to healthy patients. However, to date, it has not been studied among the different etiologies of DCM [ 26 , 27 ]. Hence, further analysis of circRNAs among DCM etiologies might provide early, precise characterization of the disease and lead to novel pathological information, beyond the traditional biomarkers.…”

Global RNA editing identification and characterization during human pluripotent-to-cardiomyocyte differentiation

“…The paired-end RNA-seq datasets of 10 CHDs, including 5 SVDs and 5 TOFs, and 5 healthy control samples were downloaded from the GEO database (GEO: GSE132401 ) performing on the Illumina NovaSeq 6000 platform 54 ( Table S2 ). Another paired-end RNA-seq dataset contained 3 human DCM samples and 3 control samples from the GEO database (GEO: GSE162505 ) 55 ( Table S2 ). The DNA/RNA variances were identified using the same method described in Figure S1 , which was the same as the identification of RNA editing during human cardiomyocyte differentiation mentioned above.…”

Circular RNA Expression for Dilated Cardiomyopathy in Hearts and Pluripotent Stem Cell–Derived Cardiomyocytes

“…Furthermore, along a clinical investigation in identifying the roles of circRNAs in cardiac systolic and diastolic function, Lin et al constructed the circRNAs-miRNA-mRNA gene regulatory networks including 9,585 circRNAs (231 upregulated and downregulated) and 22,050 mRNAs (617 upregulated and downregulated). The comprehensive dataset assessed that the downregulated mRNA would inhibit cardiac systolica, and lack of some circRNAs would lead to DCM (Lin et al, 2021).…”