**1. Introduction**

Cystic Fibrosis (CF) is a common autosomal recessive disorder. Although in its classical form CF affects several organs, including the pancreas and the gastrointestinal and reproductive tracts, its morbidity is mainly due to pulmonary damages. This disorder is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (*CFTR*) gene. This gene displays great mutational heterogeneity, depending on the ethnic and phenotypic background, with almost 2,000 referenced *CFTR* alterations (genet.sickkids.on.ca/). The most common mutation

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is the p.Phe508del, whereas other mutations, located both in coding and non-coding regions, are rare or private. The p.Phe508del mutation induces aberrant protein folding, leading to endoplasmic reticulum (ER)-associated degradation, atypical intracellular trafficking and reduced stability of the CFTR protein at the apical membrane. Dysfunction or lack of the CFTR protein causes an obstructive lung disease characterized by impaired ion transport in the airway epithelium, accumulation of sticky mucus in the air space and chronic airway inflam‐ mation. Physiological *CFTR* expression is tightly controlled by transcriptional, post-transcrip‐ tional, translational and post-translational regulatory mechanisms, resulting in complex spatial and temporal expression patterns. Notwithstanding the importance of *CFTR* transcrip‐ tional regulation [1-3], *CFTR* expression can be modulated through other mechanisms. Indeed, epigenetic changes, such as DNA methylation or histone acetylation, also influence *CFTR* gene expression in different tissues [4-7]. Post-transcriptional controls also regulate its expression, for instance via the usage of upstream open reading frames (uORFs) encoded within the *CFTR* 5'UTR [8] and the 3'UTR that controls *CFTR* mRNA stability through ARE sequences (AU-rich elements) [9]. An emerging area of research is focusing on the role played by non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), in *CFTR* gene expression. Starting from 2011, a few studies have shown the involvement of miRNAs in the physiological control of the complex spatio-temporal expression pattern of *CFTR* mRNA [10,11], including a recent work by our group [3]. Moreover, the implication of long non-coding RNAs (lncRNAs) and miRNAs in human diseases is well documented [12], including in inherited disorders [13] and lung diseases [14-17]. However, only few studies, described below, have hitherto been carried out on the role of ncRNAs in CF. This chapter is an overview of the findings about the role of ncRNAs in physiological *CFTR* gene expression and in CF.
