Differential pattern of microRNAs expression in Cystic Fibrosis and normal bronchial epithelial cells.

Cystic Fibrosis (CF) is due to mutation in the chloride channel CFTR gene causing impairment of chloride secretion in the apical membrane of epithelial cells. The most common CFTR mutation in CF is the deletion of the phenylalanine at the position 508 of the protein (DF508), leading to the retention of the mutant protein within the ER and its rapid degradation via ERAD pathway. More than 1800 mutations have been identified so far, variably affecting CFTR activity, but none of them have been clearly linked to a certain phenotype. In other words, even if carrying the same genotype, CF patients might face a different development of their disease. Clearly, CF disease also depends on other genetic and/or environmental factors. Lately, a number of studies focused on modifier genes that may determine severity of lung disease, as MBL and TGF-B. Recently, Wright et al. performed whole-genome microarrays assays of nasal cells from non-CF individuals, mild CF and DF508-CFTR homozygous patients and found a total of 652 out of 1187 genes differentially expressed in these three groups (1). MicroRNAs (miRNAs) are single-stranded RNA molecules of about 21-23 nucleotides in length which regulate gene expression. First described in 1993, miRNAs are non-coding RNA ; instead each primary transcript (a pri-miRNA) is processed into a short stem-loop structure called a premiRNA and finally into a functional miRNA. Mature miRNA molecules are partially complementary to one or more mRNA molecules, and thus down-regulate gene expression by inducing mRNA degradation or repression of protein expression by translation inhibition. Differential expression in miRNAs has been shown to influence disease development in Alzheimer’s disease, cancer, heart failure and COPD. We performed microarray analysis of miRNAs expression using primary bronchial epithelial cells from three different donors (DF/DF) and from three non-CF donors. Among the 856 miRNAs identified in the human genome at the time we performed the study, 94 were expressed in HBE cells, with 16 of them differentially expressed between CF and non CF patients : - miR22, miR29a, miR29c, miR30a, miR30b, miR30c, miR30d, miR30e, miR151-3p, miR151-5p were upregulated in CF-HBEs ; - miR103, miR107, miR146a, miR203, miR224, miR1246 were down-regulated in CF-HBEs. Real-time PCR experiments partially confirmed microarrays results, finding significant differences in expression of 11 of the 16 miRNAs. Further target analysis of the differentially expressed mi-RNAs is expected to identify new therapeutic targets in CF