Identification of differentially expressed circular RNAs during TGF-β1-induced endothelial-to-mesenchymal transition in rat coronary artery endothelial cells

Objective: Although differentially expressed circRNAs have been proposed to be closely associated with epithelial-mesenchymal transition (EMT), the roles of circRNAs remain unclear in endothelial-to-mesenchymal transition (EndMT), which is a subcategory of EMT. Herein, we characterized the expression and potential function of circRNAs during TGF-beta 1-induced EndMT in rat coronary artery endothelial cells (CAEC). Methods: High-throughput RNA sequencing was performed for unbiasedly profiling the expression of circRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis were performed using online forecasting databases. Real-time quantitative polymerase chain reaction (RT-qPCR) was used for confirming the circRNA expression obtained from the sequencing data. Results: Among the candidated circRNAs, 102 circRNAs were differentially expressed, among which 66 circRNAs and 36 circRNAs were upregulated and down-regulated, respectively, in TGF-beta 1-treated rat CAEC. GO analysis findings revealed that numerous differentially expressed circRNAs were closely associated with the biological process. KEGG signaling pathway analysis suggested that the abnormal expression of circRNAs had been implicated in regulating the dynamics endothelial cell junctions. Furthermore, we also found that three EndMT-related circRNAs, chr5:90817794 vertical bar 90827570, chr8:71336875 vertical bar 71337745, and chr6:22033342 vertical bar 22038870, were significantly up-regulated in TGF-beta 1-treated rat CAEC. Conclusion: The findings of this study reveal a comprehensive expression and potential functions of differentially expressed circRNAs during TGF-beta 1-induced EndMT. These findings provide mechanistic insights into the role of circRNAs in EndMT-related cardiovascular diseases (CVDs).