Identification of circular RNAs in human aortic valves.

With the wide application of RNA-Seq technology, thousands of circular RNAs (circRNAs) have been identified in different type of tissues and cells in many organisms, but little is known on the human aortic valve expressed circRNAs. In this study, we identified all circRNAs in two calcified human aortic valves, and characterized the features of all circRNAs. A total of 5476 circRNAs were identified in human aortic valves, including 1412 (25.79%) aortic valve specific circRNAs. Next, we showed that most aortic valve specific circRNAs were derived from the exonic regions of their host genes, and majority of the host genes contained less than three circRNAs. To predict the potential function of aortic valve specific circRNAs, we performed the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for the host genes, and identified both microRNA (miRNA) and RNA binding protein (RBP) binding sites inside aortic valve specific circRNAs. Results showed that these host genes were involved in some aortic valve related function pathways, such as ECM-receptor interaction pathway, ErbB signaling pathway, and vascular smooth muscle contraction pathway. We also found that most aortic valve specific circRNAs harbored abundant miRNA response elements (MREs), and some aortic valve specific circRNAs could bind to RBP of interest. Functional analysis suggested that these aortic valve specific circRNAs could act as post-transcriptional regulators.