Circular RNAs are differentially expressed in cystic fibrosis bronchial epithelium and are involved in regulation of ion conductance

Circular RNAs (circRNAs) are non-coding RNAs that can regulate gene expression by acting as microRNA (miRNA) sponges. Their functional roles in cystic fibrosis (CF) is unknown. Here we show that circRNAs are differentially expressed in CF vs non-CF immortalized bronchial epithelial cell (BEC) lines with two - cASH1L and cCD109 - also downregulated in adult CF primary BECs. Biochemical characterization confirmed these are true cytoplasmic circRNAs. Their over-expression did not impact the inflammatory profile of CF BEC lines, however loss- and gain-of-function studies demonstrated that cCD109 regulates ion conductance in a CFTR-independent manner in CFBE41o- cells and advanced in vitro models of CF bronchial epithelium. Pull down of cCD109 in CFBE41o- cells suggests it may bind to miRNAs. cCD109 is a circRNA with biological function in CF bronchial epithelium, and possible involvement in the pathology of CF.