Abstract
Non-coding RNAs (ncRNAs) are involved in the regulation of numerous biological processes and pathways and therefore have been extensively studied in human diseases. Previous reports have shown that non-coding RNAs play a crucial role in the pathogenesis and aberrant regulation of respiratory diseases. The altered expression of microRNAs (miRNAs) and long non-coding RNAs in blood and also locally in sputum or exhaled breath condensate influences lung function, immune response, and disease phenotype and may be used for the development of biomarkers specific for airway disease. In this review, we provide an overview of the recent works studying the non-coding RNAs in airway diseases, with a particular focus on chronic respiratory diseases of childhood. We have chosen the most common chronic respiratory condition—asthma—and the most severe, chronic disease of the airways—cystic fibrosis. Study of the altered expression of non-coding RNAs in these diseases may be key to better understanding their pathogenesis and improving diagnosis, while also holding promise for the development of therapeutic strategies using the regulatory potential of non-coding RNAs.
Highlights
Non-coding RNAs are master regulators of gene expression that influence numerous biological pathways including proliferation, differentiation, and apoptosis, as well as immune response (innate and adaptive immunity, differentiation of T and B cells, inflammation, and tissue repair and remodeling)
Housekeeping RNAs include those involved in ribosomal machinery, i.e. rRNAs, transfer RNAs, small nuclear RNAs and small nucleolar RNAs, whereas regulatory RNAs include short non-coding RNAs and long non-coding
MicroRNAs are small non-coding RNAs (18–25 nucleotides long) that regulate expression of target genes by inhibiting their translation via RNA interference [4]. They are synthesized as precursors in the nucleus, where they undergo maturation with several enzymatic reactions and are translocated to the cytoplasm where they exert their biological function in a protein complex
Summary
Non-coding RNAs (ncRNAs) are master regulators of gene expression that influence numerous biological pathways including proliferation, differentiation, and apoptosis, as well as immune response (innate and adaptive immunity, differentiation of T and B cells, inflammation, and tissue repair and remodeling (reviewed by [1])). The most commonly RNAs studied in respiratory diseases are short ncRNAs (mainly microRNAs, but recently piwi-interacting RNAs (piRNAs) and long ncRNAs. MicroRNAs (miRNAs) are small non-coding RNAs (18–25 nucleotides long) that regulate expression of target genes by inhibiting their translation via RNA interference [4]. It has been predicted that, in humans, about 60% of mRNAs are targets for miRNA [5] and one miRNA may target more than 100 mRNAs [6] Another group of small RNAs are piRNAs that play an important role in germline cells. Another interesting feature is that they may be expressed in both sense and antisense orientation relative to protein-coding genes [9] Studies demonstrated that they are regulators of different cellular processes including chromatin structure changes, transcription and post-transcriptional processing, and intracellular trafficking [10]. This review will focus on the two most common chronic childhood diseases of the airways, which have different genetics backgrounds: polygenic asthma, and monogenic cystic fibrosis, with particular emphasis on the central role of airway epithelium in the pathogenesis of these diseases and responses to environmental stimuli
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