F. Sonneville, M. Ruffin, H. Corvol and O. Tabary
CDR St Antoine, Hôpital Saint Antoine, Paris, France
Impairment of the CFTR chloride channel activity in cystic fibrosis (CF) patients is the main cause of the deterioration of lung function. The chloride channel ANO1 was proposed as a potential therapeutic target in CF. Recently, we have shown that ANO1 activity and expression were reduced in a CF context (Ruffin et al., 2013). Our objective is to understand the origin of these decreases studying miRNAs.
We identified miR-9 as ANO1 regulator. We observed miR-9 overexpression in CF cells and a decrease of ANO1 expression and chloride activity when we overexpress miR-9. In CF, it would be interesting to increase ANO1 activity, so we have done experiments using antisense oligonucleotides designed to specifically prevent miR-9 fixation on ANO1 (TSB ANO1). We observed an increase of ANO1 chloride activity and expression using the TSB ANO1 in CF cell lines and CF primary human bronchial epithelial cells.
Our results showed that miR-9 directly regulates ANO1 and that in CF, use of TSB ANO1 restores ANO1 expression, chloride activity and migration. We now evaluate the possibility to use TSB in therapeutics.