miR-144-3p Is a Biomarker Related to Severe Corticosteroid-Dependent Asthma

Abstract

MicroRNAs are non-coding molecules that act both as regulators of the epigenetic landscape and as biomarkers for diseases, including asthma. In the era of personalized medicine, there is a need for novel disease-associated biomarkers that can help in classifying diseases into phenotypes for treatment selection. Currently, severe eosinophilic asthma is one of the most widely studied phenotypes in clinical practice, as many patients require higher and higher doses of corticosteroids, which in some cases fail to achieve the desired outcome. Such patients may only benefit from alternative drugs such as biologics, for which novel biomarkers are necessary. The objective of the study was to study the expression of miR-144-3p in order to discover its possible use as a diagnostic biomarker for severe asthma. For this purpose, miR-144-3p was evaluated in airway biopsies and serum from asthmatics and healthy individuals. mRNA was studied in asthmatic biopsies and smooth muscle cells transfected with miR-144-3p mimic. An in silico regulation of miR-144-3p was performed using miRSystem, miRDB, STRING, and ShinyGO for pathway analysis. From our experimental procedures, we found that miR-144-3p is a biomarker associated with asthma severity and corticosteroid treatment. MiR-144-3p is increased in asthmatic lungs, and its presence correlates directly with blood eosinophilia and with the expression of genes involved in asthma pathophysiology in the airways. When studied in serum, this miRNA was increased in severe asthmatics and associated with higher doses of corticosteroids, thereby making it a potential biomarker for severe asthma previously treated with higher doses of corticosteroids. Thus, we can conclude that miR-144-3p is associated with severe diseases in both the airways and serum of asthmatics, and this association is related to corticosteroid treatment.

Analysis of Differentially Expressed MicroRNAs in Serum and Lung Tissues from Individuals with Severe Asthma Treated with Oral Glucocorticoids

“…Our group previously used NGS to describe 15 miRNAs differentially expressed between eosinophilic and non-eosinophilic asthmatic patients, two of which were validated and could serve as instruments to classify patients into different phenotypes/endotypes [ 15 ]. In addition, hsa-miR-144-3p was previously described by our group to present an increase in miRNA levels in corticosteroid treated subjects by RT-qPCR [ 27 ], which validates the result obtained in miRNAs-Seq from the lung biopsy samples of asthmatics.…”

Advances and Highlights of miRNAs in Asthma: Biomarkers for Diagnosis and Treatment

“…Faiz et al used airway biopsies from subjects with COPD and reported elevated miR-320d during ICS treatment compared to placebo, as this miRNA reduced cigarette smoke extract-induced inflammation by NF-κβ inhibition [ 106 ]. Regarding this matter, we found that expression of miR-144-3p was increased in the serum and lung tissue of asthmatics, and that this expression augmented with corticosteroids, hence making it a biomarker for severe asthma treated with higher doses of corticosteroids (AUC = 0.74) [ 107 ].…”

The Potential Role of Serum and Exhaled Breath Condensate miRNAs in Diagnosis and Predicting Exacerbations in Pediatric Asthma

“…Another study demonstrated a higher concentration of miRNA-144-3p in severe disease and its positive correlation with blood eosinophilia. This biomolecule affects genes responsible for the inflammatory process and remodeling of the airways, e.g., GATA3, STAT6, SOCS5, RHOA, NR3C1, and PTEN, which makes it a potential diagnostic marker for severe asthma [ 20 ]. In non-allergic asthma, miRNA-629-3p, miRNA-223-3p, and miRNA-142-3p were significantly elevated in patients with severe symptoms and associated with increased inflammation mediated by neutrophils.…”