MicroRNA-21 as a novel biomarker in diagnosis and response to therapy in asthmatic children

Abstract

Background: The underlying molecular mechanisms leading to asthma remain largely unclear. MicroRNAs (miRNAs) are short noncoding RNAs exert powerful effects on immunological function by tuning networks of target genes that orchestrate cell activity. However, the role of miRNAs, specifically microRNA-21 (miRNA- 21), in the regulation of allergic airway inflammation is not well defined. Our aim was to investigate the serum miRNA- 21 expression levels as potential biomarker in childhood asthma [with, without inhaled corticosteroid (ICS) therapy, and steroid resistant (SR)]; and their possible contributions in disease status, its molecular target interleukin-12 (IL-12) p35, and response to therapy.

Materials and methods: This study included 175 children; 95 were asthmatic patients subdivided into 3 groups [40 asthmatic children without ICS, 40 steroid sensitive (SS) asthma children and 15 steroid resistant (SR) asthma children] and 80 were healthy children as healthy controls. The miRNA-21 expressions levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) in all children. Serum IL-12p35 and total IgE levels were measured using enzyme-linked immunosorbent assay (ELISA).

Results: The expression levels of miRNA-21 were significantly higher in the asthmatic children than in control group (P<0.001); with significantly higher levels in asthmatic patients without ICS or in SR patients compared to SS children (P<0.001). On contrast, serum IL-12p35 levels were significantly decreased in asthmatic patients without ICS therapy or in SR asthma patients as compared to SS patients (P<0.001). Our data revealed that serum miRNA-21 expression levels was significant negatively correlated with serum IL-12p35 levels and FEV1, while it was positively correlated with both sputum and blood eosinophils. Importantly, serum miRNA-21 had a predictive value in differentiating SS from SR patients, with an AUC value of 0.99, specificity of 86.7%, sensitivity of 97.5% and P<0.001.

Conclusion: This study suggested that serum miRNA-21 is stable and detectable in serum of asthmatic children, which could promise potential biomarker in diagnosis as well as in response to therapy of asthma.

Keywords: Asthma; Real-time polymerase chain reaction; Steroid therapy; miRNA; miRNA -21.