Abstract
BackgroundAs the most frequent type of cyanotic congenital heart disease (CHD), tetralogy of Fallot (TOF) has a relatively poor prognosis without corrective surgery. Circular RNAs (circRNAs) represent a novel class of endogenous noncoding RNAs that regulate target gene expression posttranscriptionally in heart development. Here, we investigated the potential role of the ceRNA network in the pathogenesis of TOF.MethodsTo identify circRNA expression profiles in TOF, microarrays were used to screen the differentially expressed circRNAs between 3 TOF and 3 control human myocardial tissue samples. Then, a dysregulated circRNA-associated ceRNA network was constructed using the established multistep screening strategy.ResultsIn summary, a total of 276 differentially expressed circRNAs were identified, including 214 upregulated and 62 downregulated circRNAs in TOF samples. By constructing the circRNA-associated ceRNA network based on bioinformatics data, a total of 19 circRNAs, 9 miRNAs, and 34 mRNAs were further screened. Moreover, by enlarging the sample size, the qPCR results validated the positive correlations between hsa_circ_0007798 and HIF1A.ConclusionsThe findings in this study provide a comprehensive understanding of the ceRNA network involved in TOF biology, such as the hsa_circ_0007798/miR-199b-5p/HIF1A signalling axis, and may offer candidate diagnostic biomarkers or potential therapeutic targets for TOF. In addition, we propose that the ceRNA network regulates TOF progression.
Highlights
As the most frequent type of cyanotic congenital heart disease (CHD), tetralogy of Fallot (TOF) has a relatively poor prognosis without corrective surgery
Current knowledge and understanding have shown that temporal and spatial expression patterns of heart development-related genes are essential in the regulation of cardiomyogenesis, which means that both genetic and epigenetic factors play a crucial role throughout development [8, 9]
Box plots were constructed to show the distribution of Circular RNA (circRNA) expression profiles
Summary
As the most frequent type of cyanotic congenital heart disease (CHD), tetralogy of Fallot (TOF) has a relatively poor prognosis without corrective surgery. Circular RNAs (circRNAs) represent a novel class of endogenous noncoding RNAs that regulate target gene expression posttranscriptionally in heart development. We investigated the potential role of the ceRNA network in the pathogenesis of TOF. Numerous studies have shown that miRNA expression should be disordered in TOF heart tissues [7]. Current knowledge and understanding have shown that temporal and spatial expression patterns of heart development-related genes are essential in the regulation of cardiomyogenesis, which means that both genetic and epigenetic factors play a crucial role throughout development [8, 9]. Microarray can only explore known circRNAs. To identify novel circRNAs, next-generation sequencing technology is a suitably sensitive tool
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