microRNAs profiling in Cystic Fibrosis bronchial epithelial cells: a pilot study to identify new therapeutic targets
(2010) 24th annual North american Cystic Fibrosis Conference — Location: Baltimore, MD, USA (21.October.2010)
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- Abstract
- Cystic fibrosis (CF) is due to mutations 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 (ΔF508), leading to the retention of CFTR in the ER and its rapid degradation via ERAD pathway. More than 1700 mutations have been identified so far, variably affecting CFTR activity but none of them have been clearly linked to a certain pathophysiology. In other words, even if carrying the same genotype, CF patients might face a different development in their disease. Clearly, CF disease also depends on other genetic and/or environmental factors. Lately, a number of studies focus on modifier genes that may determine severity of lung disease, as e.g. Mannose Binding Lectin and Transforming Growth Factor beta. Recently, Wright et al. performed whole-genome microarrays assays of nasal cells from non-CF individuals, mild CF and homozygous ΔF508- CFTR 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 messenger RNA (mRNA) molecules, and thus down-regulate gene expression by inducing mRNA degradation or protein expression by translation inhibition. Differential expression in miRNAs has been shown to influence disease development in Alzheimer’s, cancer, heart failure and COPD. No systematic analysis of miRNA expression in CF has been reported to date, although one study showed a down-regulation of miR-126 in CF airway epithelial cells (2). We performed microarray analysis of miRNAs expression using primary bronchial epithelial cells from three CF donors (ΔF/ΔF) and from three non-CF donors. Among the 856 miRNAs identified in the human genome at the time, 94 were expressed in HBE cells with 16 of them differentially expressed between CF and non-CF patients. The following table summarizes the microarrays results. Real-time PCR experiments partially confirmed microarray results, finding significant differences in expression of 11 of the 16 miRNAs. Further target analysis of the differentially expressed miRNAs is expected to identify new therapeutic targets in CF. Supported by the Cystic Fibrosis Foundation
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Noël, S., Latoche, J., Harvey, P., Pilewski, J., & Frizzell, R. (2010). microRNAs profiling in Cystic Fibrosis bronchial epithelial cells: a pilot study to identify new therapeutic targets. Pediatric Pulmonology, 45(s33), 284. https://hdl.handle.net/2078.5/42546 (Original work published 2010)