MicroRNAs as Diagnostic and Therapeutic Biomarkers in Childhood Asthma: A Systematic Review with Bioinformatics...

Background: MicroRNAs (miRNAs) are stable, small non-coding RNAs involved in asthma-related pathways and are promising diagnostic biomarkers and therapeutic targets in childhood asthma. Objective: To identify miRNAs differentially expressed in preschool wheezing and childhood asthma, evaluate their association with asthma diagnosis and severity-related phenotypes, and explore their potential translational relevance through exploratory bioinformatic analyses. Methods: A systematic search of Medline, Embase, SCOPUS, PubMed, CINAHL, and Web of Science was conducted for English-language articles published up to March 19, 2025. Eligible human studies reported that miRNAs were differentially expressed in children with wheeze or asthma versus healthy controls (p < 0.05, fold change ≥ 1.5). Bioinformatic analysis identified hub genes, constructed protein-protein interaction networks, and predicted drug-gene interactions. Results: Forty-seven studies met the inclusion criteria, yielding 58 differentially expressed miRNAs (31 up, 27 down). Recurrently reported miRNAs included miR-497, let-7e, miR-98, miR-21, miR-126a, miR-196a2, miR-1, miR-146a-5p, miR-210-3p, miR-145-5p, and miR-200c-3p across blood, nasal swabs, BALF, and exhaled breath condensate. miR-26a showed strong diagnostic performance (sensitivity 83%, specificity 93%; p < 0.002, 95% CI 0.831-0.987). Functional enrichment implicated 56 differentially expressed genes in metabolic and immune processes. Ten hub genes (including TNF, IL5, IL13, TLR4) were linked to 339 potential therapeutic agents; the exploratory network analysis highlighted overlap between predicted miRNA-regulated hub genes and existing asthma-relevant drug targets, including approved biologics. Conclusions: Our review findings suggest that several miRNAs are promising candidate biomarkers for childhood asthma phenotyping and severity assessment; however, their diagnostic utility remains exploratory and requires rigorous external validation and standardisation before clinical application.