Construction and Investigation of a circRNA-Associated ceRNA Regulatory Network in Tetralogy of Fallot

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background: </jats:bold>As the most frequent type of cyanotic congenital heart diseases (CHD), Tetralogy of Fallot (TOF) has a relatively poor prognosis without the corrective surgery. Circular RNA (circRNA) represents a novel class of endogenous noncoding RNAs that regulate target gene expression post-transcriptionally in heart development. Here, we investigate the potential role of ceRNA network in the pathogenesis of TOF. <jats:bold>Methods:</jats:bold> To identify circRNAs expression profiles in Tetralogy of Fallot, microarrays were used to screen the differentially expressed circRNA between 3 TOF and 3 control human myocardial tissue samples. Then, a dysregulated circRNA- associated ceRNA network was constructed via using the established multi-step screening strategy.<jats:bold>Results:</jats:bold> In summary, total 276 differentially expressed circRNAs were identified, including 214 up-regulated and 62 down-regulated ones in TOF samples. By constructing the circRNA-associated ceRNA network based on the bioinformatics data, a total of 19 key circRNAs, 9 key miRNAs and 34 key mRNAs were further screened. Moreover, by enlarging the samples size, the qPCR results validated that the positive correlations between hsa_circ_0007798 and<jats:italic> HIF1A</jats:italic>.<jats:bold>Conclusions: </jats:bold>The findings in this study provide a comprehensive understanding of the ceRNA network involved in TOF biology, such as hsa_circ_0007798/miR-199b-5p/<jats:italic>HIF1A</jats:italic> signal axis, and may offer candidate diagnostic biomarkers or potential therapeutic targets for TOF. In addtion, we propose that the ceRNA network regulates TOF progression.</jats:p>