Research Article: miRNA profiling shows shared signatures in pediatric asthma, obesity and their comorbidity
Abstract:
Childhood obesity is a known risk factor for asthma and contributes to increased disease severity and reduced corticosteroid responsiveness. However, the molecular mechanisms underlying this comorbidity remain unclear. Using a cross-sectional design, we aimed to identify microRNA (miRNA) signatures associated with asthma–obesity comorbidity in children to shed light on potential shared molecular drivers.
Whole blood samples were collected from four pediatric groups: normal weight with asthma (NW-A, n = 11), overweight/obesity with asthma (OO-A, n = 10), overweight/obesity without asthma (OO, n = 10), and normal weight without asthma (NW, n = 12). Circulating miRNA profiles were assessed using the NanoString nCounter platform. Differential expression and pathway enrichment analyses were performed using Enrichr and other bioinformatic tools. Correlation with clinical and cytokine data was assessed by Pearson’s correlation and multiple regression analyses.
miRNA expression profiles differed markedly across the four groups. Five miRNAs (miR- 423-3p, -92a-3p, -4536-5p, -197-3p, -891a-5p) were consistently upregulated, and two (miR-144-3p, -641) were downregulated across asthma alone, obesity alone, and asthma-obesity comorbidity. Target gene analysis of OO-A-associated miRNAs highlighted involvement in IL-4, IL-13, and PIP3/AKT signaling, as well as pathways linked to innate immunity and metabolism. In OO-A, miRNA dysregulation was correlated with elevated neutrophils, pro-inflammatory cytokines, and reduced lung function.
In this exploratory study, we identified a shared circulating miRNA signature in asthma–obesity comorbidity. These miRNAs may serve as biomarkers and potential therapeutic targets for stratifying and managing asthma in children with obesity, pending validation in longitudinal studies.
Introduction:
Asthma is a heterogeneous inflammatory lung disease that affects approximately 300 million people worldwide and is characterized by airway inflammation and impaired lung function ( 1 , 2 ). Obesity is a significant contributing factor to childhood asthma. A meta-analysis by Malden et al. reported that obesity increases the incidence of asthma by 50% ( 3 ). Moreover, increased adiposity before the age of six is linked to a higher risk of developing childhood asthma ( 4 ). These two conditions interact in ways that…
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