The Interplay between MiRNAs and LncRNAs in the Pathogenesis of Asthmatic Diseases

Asthma affects people of all ethnicities and ages and there has been a substantial increase in the prevalence of asthma over the past few decades, with current estimates of approximately 300 million people suffering from the disease worldwide. The initial response consists primarily of airway smooth muscle constriction and airway inflammation (oedema, inflammatory cell infiltration, increased airway secretions). Whereas more chronic responses such as structural remodelling of the airway including smooth muscle and sub-mucosal gland hyperplasia and hypertrophy, extracellular matrix (ECM) deposition and angiogenesis are generally thought to occur in parallel with inflammatory responses. Asthma is commonly associated with a Th2 response with infiltration of eosinophils, mast cells and Th2 lymphocytes into the airways, as well as elevated serum immunoglobulin IgE levels,and is determined by interaction of multiple genes and environmental factors. MicroRNAs (miRNAs) are small non-coding RNAs of 18–25 nucleotides, that have been shown to regulate gene expression at the translational level via the RNA interference pathway. In most circumstances, miRNAs are believed to either repress mRNA translation or induce the degradation of target mRNA. Since asthma is characterised by chronic inflammation of the airways, it is likely that miRNAs might be important in the pathogenesis of the disease through modulation of immune cells. Long non-coding RNAs are a heterogeneous group of non-coding RNAs with regard to origin and mechanism of action/function. Another interesting feature is that they may be expressed in both sense and antisense orientation relative to protein-coding genes. Studies demonstrated that they are regulators of different cellular processes including chromatin structure changes, transcription and post-transcriptional processing, and intracellular trafficking. The interplay between these two different types of ncRNAs is only starting to be known but appears to be very promising for a better knowledge of the asthma pathogenesis, and therefore is becoming an exciting challenge in a therapeutic perspective; this challenge will be faced by the BI(G)MED via the use of ultra-low doses of these molecules of ncRNAs in the treatment of the asthmatic disease.

Keywords: nc RNAs, microRNAs, lnc RNAs, TH2-regulation, asthma therapy.