The Role of Non-Coding RNAs in the Pathogenesis of Asthma

Abstract

Asthma is a chronic inflammatory airway disease characterized by considerable clinical and molecular heterogeneity, involving complex interactions between genetic susceptibility, environmental factors, and immune dysregulation. Increasing evidence indicates that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other regulatory RNA species, play essential roles in the development and progression of asthma—modulate inflammatory responses, immune cell differentiation, airway remodeling, and epithelial barrier function by interacting with key molecular and signaling pathways, notably the NF-κB, JAK/STAT, PI3K/AKT/mTOR, and TGF-β/Smad cascades. For example, miR-125b-5p and miR-223-3p demonstrate consistent dysregulation across varying biological compartments and independent cohorts, while miR-21, miR-146a, miR-155, and lncRNAs like NEAT1 and MALAT1 are frequently confirmed as central regulators of airway pathology. Aberrant expression of these ncRNAs has been associated with distinct asthma phenotypes, disease severity, and therapeutic responses, highlighting their potential as diagnostic and prognostic biomarkers. This review summarizes current knowledge on the biological functions of ncRNAs in asthma, their involvement in critical pathogenic mechanisms, and discusses their emerging clinical applications and the challenges of translating RNA-based therapeutics into clinical practice.