Source: International Congress 2014 – Novel epigenetic regulators for targeting via nanomedicine
Disease area: Airway diseases

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that modulate target gene expression via translational repression or degradation of their target RNAs. MiRNAs may regulate up to one-third of all protein coding genes in human genome and dysregulation of miRNAs may contribute to cystic fibrosis (CF) pathology. Recent work has identified unique miRNA profiles in the CF lung and analysis of target genes has revealed important roles for miRNAs in the regulation of CFTR expression and function and inflammation. MiR-31 is one of the most highly expressed miRNAs present in human non-CF airway epithelial cells but its role in pulmonary epithelial cell function is unknown. In this study, we evaluated miR-31 expression in CF pulmonary epithelial cells and found that miR-31 levels were significantly decreased in CF tracheal and bronchial epithelial cell lines, primary epithelial cells and bronchial brushings compared to non-CF controls. In silico analysis predicted that the transcription factor IRF-1 was a target of miR-31 and overexpression of miR-31 in CF bronchial epithelial cells (CFBEs) resulted in a decrease in the levels of IRF-1. Furthermore, this decrease in IRF-1 was associated with a significant decrease in the expression and production of the IRF-1 target gene, the cysteine cathepsin, cathepsin S. The miR-31/IRF-1/CTSS pathway may play a functional role in the pathogenesis of CF lung disease and may open up new avenues for exploration in the search for an effective therapeutic target.

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S. Weldon, I. Ogelsby, C. Wohlford-Lenane, J. Bartlett, G. McElvaney, C. Greene, P. McCray Jr, C. Taggart (Belfast, United Kingdom; Dublin, Ireland; Iowa City, United States Of America). MiR-31 regulates IRF-1 function in cystic fibrosis epithelial cells. Eur Respir J 2014; 44: Suppl. 58, 200

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