{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:28:48Z","timestamp":1785432528770,"version":"3.56.0"},"reference-count":88,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000362","name":"Asthma-Lung UK","doi-asserted-by":"publisher","award":["ECSG24\\45"],"award-info":[{"award-number":["ECSG24\\45"]}],"id":[{"id":"10.13039\/501100000362","id-type":"DOI","asserted-by":"publisher"}]},{"award":["ECSG24\\45"],"award-info":[{"award-number":["ECSG24\\45"]}],"id":[{"id":"https:\/\/ror.org\/03z7xev21","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>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 &lt; 0.05, fold change \u2265 1.5). Bioinformatic analysis identified hub genes, constructed protein\u2013protein interaction networks, and predicted drug\u2013gene 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 &lt; 0.002, 95% CI 0.831\u20130.987). 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.<\/jats:p>","DOI":"10.3390\/jpm16040179","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:05:49Z","timestamp":1775563549000},"page":"179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MicroRNAs as Diagnostic and Therapeutic Biomarkers in Childhood Asthma: A Systematic Review with Bioinformatics Analysis"],"prefix":"10.3390","volume":"16","author":[{"given":"Ahmed I.","family":"Alrefaey","sequence":"first","affiliation":[{"name":"School of Technology and Maritime Industries, Southampton Solent University, Southampton SO14 0YN, UK"},{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0999-7190","authenticated-orcid":false,"given":"Elena V.","family":"Vorobeva","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5387-1999","authenticated-orcid":false,"given":"Jamil","family":"Jubrail","sequence":"additional","affiliation":[{"name":"School of Technology and Maritime Industries, Southampton Solent University, Southampton SO14 0YN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6169-3247","authenticated-orcid":false,"given":"Ibemusu Michael","family":"Otele","sequence":"additional","affiliation":[{"name":"School of Technology and Maritime Industries, Southampton Solent University, Southampton SO14 0YN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikaela","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Technology and Maritime Industries, Southampton Solent University, Southampton SO14 0YN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Sanchez-Elsner","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Hasan","family":"Arshad","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"},{"name":"NIHR Southampton Biomedical Research Centre, University Hospitals Southampton, Southampton SO16 6YD, UK"},{"name":"The David Hide Asthma & Allergy Research Centre, Isle of Wight PO30 5TG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1588-2400","authenticated-orcid":false,"given":"Ramesh J.","family":"Kurukulaaratchy","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"},{"name":"NIHR Southampton Biomedical Research Centre, University Hospitals Southampton, Southampton SO16 6YD, UK"},{"name":"The David Hide Asthma & Allergy Research Centre, Isle of Wight PO30 5TG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1684-9207","authenticated-orcid":false,"given":"Mohammed Aref","family":"Kyyaly","sequence":"additional","affiliation":[{"name":"School of Technology and Maritime Industries, Southampton Solent University, Southampton SO14 0YN, UK"},{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1111\/all.15054","article-title":"Advances and highlights in asthma in 2021","volume":"76","author":"Agache","year":"2021","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"w14036","DOI":"10.4414\/smw.2014.14036","article-title":"Childhood asthma: Causes, risks, and protective factors; a role of innate immunity","volume":"144","author":"Noutsios","year":"2014","journal-title":"Swiss Med. 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