Long non-coding RNAs in the CFTR locus: New transcriptional regulators of CFTR gene expression.

Cystic fibrosis (CF) is caused by mutations in the tightly regulated cystic fibrosis transmembrane regulator (CFTR) gene. The CFTR gene is weakly expressed in adult tissues, and its locus contains elements that regulate its mRNA and protein expression. Here, we identified new long non-coding RNAs (lncRNAs) transcribed from the CFTR locus that are differentially expressed in human tissues. In particular, we focused on the CF006 lncRNA, which stimulates CFTR transcription and increases mRNA and protein expression and was strongly downregulated in bronchial epithelium reconstituted from CF-derived airway epithelial cells. Our findings also suggest that CF006 may act directly by binding to the CFTR promoter and/or indirectly by affecting the local binding of transcription factors. Moreover, CF006 lncRNA expression was negatively regulated by miR-145, a microRNA (miRNA) upregulated in CF. Altogether, our findings suggest that the lncRNA CF006 is a new cis-regulatory element of CFTR expression and, therefore, a candidate therapeutic target for CF.