Non-Coding RNAs in Airway Diseases: A Brief Overview of Recent Data

Abstract

Inflammation of the human lung is mediated in response to different stimuli (e.g., physical, radioactive, infective, pro-allergenic, or toxic) such as cigarette smoke and environmental pollutants. These stimuli often promote an increase in different inflammatory activities in the airways, manifesting themselves as chronic diseases (e.g., allergic airway diseases, asthma chronic bronchitis/chronic obstructive pulmonary disease, or even lung cancer). Non-coding RNA (ncRNAs) are single-stranded RNA molecules of few nucleotides that regulate the gene expression involved in many cellular processes. ncRNA are molecules typically involved in the reduction of translation and stability of the genes of mRNAs s. They regulate many biological aspects such as cellular growth, proliferation, differentiation, regulation of cell cycle, aging, apoptosis, metabolism, and neuronal patterning, and influence a wide range of biologic processes essential for the maintenance of cellular homeostasis. The relevance of ncRNAs in the pathogenetic mechanisms of respiratory diseases has been widely established and in the last decade many papers were published. However, once their importance is established in pathogenetic mechanisms, it becomes important to further deepen the research in this direction. In this review we describe several of most recent knowledge concerning ncRNA (overall miRNAs) expression and activities in the lung.

Keywords: COPD; asthma; extracellular vesicles; lung cancer; microRNAs; pollutions.

Figure 1

Representation of the etiology, inflammation, and symptoms of chronic inflammatory diseases of the lung. Asthma and COPD are diseases with similarities. However, they are different regarding etiology, type of inflammatory cells, mediators, consequences of inflammation.

Figure 2

Schematic representation of the general steps of miRNA biogenesis. The biogenesis of miRNAs starts in the nucleus with the processing of RNA polymerase II/III transcripts post- or co-transcriptionally into pri-miRNAs. Then, a ribonuclease III enzyme transforms the pri-miRNAs in pre-miRNAs, which are transported into the cytoplasm by Exportin 5 (XPO5)/RanGTP complex action. Reaching the cytoplasm pre-miRNA is transformed in mature miRNA/miRNA* duplex by RNase III endonuclease Dicer and the RNA-binding protein TRBP the action. miRNA then forms a miRNA-mRNA RISC complex to induce mRNA degradation or translational repression.

Figure 3

Schematic panel describing nc-RNAs involved in airway diseases and indicated in the review. The miRNAs and lnc-RNAs are expressed in lung diseases such as asthma, COPD, LC, or in lung diseases associated with environmental pollution.

Figure 4

Cells of the lung release EVs of different size containing proteins, lipids, and nucleic acid involved in the mechanisms of cell–cell communication underlies the immunological response of respiratory disease such as asthma, COPD, LC, and airway diseases related to pollutions. EVs content show promise as diagnostic biomarkers and therapeutic targets in several lung diseases. BALF- and lung-tissue-derived EVs of healthy non-smokers, smokers have a miRNA profile with three differently expressed miRNAs in BALF, and one in the lung-derived EVs from COPD patients as compared to healthy non-smokers. MiR-122-5p is three- or five-fold downregulated among the lung-tissue-derived EVs of COPD patients as compared to healthy non-smokers and smokers, respectively. These data strongly suggest that miRNAs in the lungs of subjects with chronic lung diseases might be considered as potential biomarkers useful for therapeutic targets [121].