%0 Journal Article %A Irene Oglesby %A Shane O'Neill %A Noel McElvaney %A Catherine Greene %T A three miRNA signature regulates the CF transmembrane conductance regulator (CFTR) in cystic fibrosis airway epithelium %D 2011 %J European Respiratory Journal %P 1446 %V 38 %N Suppl 55 %X Expression profiling studies have identified altered miRNA patterns in several human diseases, however little is known of the role miRNA play in cystic fibrosis (CF). Here we examined the impact of altered miRNA expression in CF bronchial epithelium on CFTR expression.We performed miRNA expression profiling on bronchial brushings taken from five CF and five non-CF individuals by qRT-PCR using Taqman Low Density Arrays (TLDAs). Expression of altered miRNA was validated by qRT-PCR in additional brushings and in vitro in CF and non-CF bronchial epithelial cell lines. CFTR gene expression was also measured. miRNA inhibition and over-expression studies were performed in CFBE41o– and 16HBE14o– cell lines respectively in vitro and CFTR mRNA and protein was detected by qRT-PCR and western blot.Of the 667 miRNA examined 56 were down-regulated and 36 up-regulated in CF. Using in silico analysis we identified miRNAs predicted to target the CFTR gene that were collectively up-regulated in the CF samples e.g. a three miRNA signature consisting of miR-145, miR-223 and miR-494. Knockdown of miR145, -223 and -494 in CFBE41o– cells led to an increase in CFTR protein production. Conversely a decrease in CFTR expression was observed following miRNA over-expression in 16HBE14o– cells. CFTR mRNA expression was significantly decreased in CF vs. non-CF bronchial brushings.These data show that miRNA are differentially expressed in the CF airway epithelium, miRNA targeting CFTR are up-regulated and CFTR is reciprocally down-regulated. The regulation of CFTR by miRNA may represent an additional endogenous level of control over mutant CFTR in classes I, II or V CFTR mutations. %U