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. 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