MicroRNA global profiling in cystic fibrosis cell lines reveals dysregulated pathways related with oncogenesis, inflammation, growth and glucose metabolism. MicroRNA global profiling in cystic fibrosis cell lines reveals dysregulated pathways related with oncogenesis, inflammation, growth and glucose metabolism

Global profiles of 754 human miRNAs from CFBE41o- (F508del/F508del), and IB3 (F508del/W1282X) cell lines, carrying the most common mutations for Cystic Fibrosis, were analysed. 16HBE14o- cells, derived from normal bronchus, were used as calibrator. The relative abundance of each miRNA was calculated and fold-changes≥+2 or ≤-2 (p-value≤0.05) were considered significant. MiRNA target genes and KEGG pathways were identified using miRWalk v.3 and DIANA-mirPath v3.0, respectively and a protein-protein interaction network was performed by STRING 11.0. In CF cell lines 41 miRNAs showed significant changes. Eight miRNAs were regulated in CFBE41o- only and 23 in IB3 only, suggesting genotype-specific effects. Five miRNAs were up-regulated and 1 down-regulated in both CFBE41o- and IB3. The 41 miRNAs regulated genes within pathways involved with cancer, inflammation, body growth, glucose metabolism and lipid metabolism. Interestingly, key genes involved with Ras, TGF-beta, Jak-Stat and insulin signaling were highlighted. Overall design: miRNA expression profiling was performed on total RNA, including small RNAs, purified from each cell line in two replicates. Cell lines 16HBE14o- constitutes the healthy control, CFBE41o- are the model for the homozygous mutation of the CFTR gene responsible of cystic fibrosis, IB3 are the model for the hetorozygote mutation