The molecular mechanisms that drive the CFTR gene expression remain unclear. We identified a myriad of transcription factors that play a crucial role in lung formation (FOX, C/EBP, NKX2). We have also showed that some miRNAs control the stability of CFTR transcripts through their binding to their cognate binding motifs in the 3’UTR part of the CFTR gene such as miR-101 and miR-145 (article in submission).
In this project we propose to better define how the identified miRNAs modulate the expression of the CFTR gene. Because it exists a connection between expression and regulation of the miARNs and the transcription factors, we plan to determine putative link between regulatory elements that have been showed to control the CFTR expression. Finally, we have recently showed that use of oligonucleotides targeting binding sites of certain miRNAs increases the level of CFTR transcripts in Air-Liquid Interface cell culture model from nasal cells.
Identification of new regulatory motifs will contribute to a better understanding of the molecular mechanism controlling the CFTR expression and will offer new therapeutic targets.