{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:50:50Z","timestamp":1784224250710,"version":"3.55.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["201244\/Z\/16\/Z"],"award-info":[{"award-number":["201244\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide and currently lacks effective disease-modifying therapies. Extracellular vesicles (EVs) are key mediators of intercellular communication and transport biologically active cargo, including microRNAs (miRNAs). We previously identified 8 differentially expressed EV miRNA (miR-223-3p, miR-2110, miR-182-5p, miR-200b-5p, miR-625-3p, miR-204-5p, miR-138-5p and miR-338-3p) that were differentially expressed in individuals with COPD compared with healthy volunteer ex-smoker controls (HV-ES). This study aimed to identify miRNA\u2013mRNA interactions in diseased lung epithelium that may contribute to COPD pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Gene expression was quantified by RNA sequencing of epithelial brushings obtained from 24 subjects with COPD and 20 HV-ES.\n                      <jats:italic>In silico<\/jats:italic>\n                      analyses were performed to identify target genes of the previously identified EV-derived miRNAs isolated from the same individuals. MiRNA\u2013mRNA interactions were examined using negative correlation analysis and network-based approaches, and enrichment of biological processes was assessed using Cytoscape. Associations between computer tomography (CT) disease probability measures (DPM) and gene expression were assessed using Spearman correlation across the pooled cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 191 genes were differentially expressed in epithelial brushings from subjects with COPD compared with HV-ES.\n                      <jats:italic>In silico<\/jats:italic>\n                      analysis identified 121 miRNA\u2013mRNA interactions involving these genes and the EV-associated miRNAs. Network analysis revealed miR-182-5p as a central hub, targeting multiple highly differentially expressed genes (DEGs). Expression of these DEGs correlated with CT DPM of emphysema and small airways disease (SAD). Exploratory pathway analyses suggested potential trends toward coordinated network regulation involving metabolic and immune \u2013related processes; however, no biological processes remained significant after correction for multiple testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings highlight a potential role for EV-derived miRNA\u2013mRNA regulatory networks in COPD pathogenesis, with miR-182-5p emerging as a putative regulator within this network. While exploratory analyses suggested possible associations with metabolic and immune-related pathways, these did not withstand multiple testing correction and should therefore be interpreted as hypothesis-generating. These findings support further mechanistic investigation of EV-derived miRNA\u2013mRNA regulatory networks in COPD and may help inform future translational studies exploring their biological relevance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1743277","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:38:56Z","timestamp":1782106736000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated miRNA\u2013mRNA network analysis identifies miR-182-5p as a potential regulator in COPD pathogenesis"],"prefix":"10.3389","volume":"13","author":[{"given":"Hannah","family":"Burke","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Southampton","place":["Southampton, United Kingdom"]},{"name":"NIHR Southampton Biomedical Research Centre, University Hospital Southampton","place":["Southampton, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodie","family":"Ackland","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton","place":["Southampton, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian R.","family":"Angermann","sequence":"additional","affiliation":[{"name":"Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, Biopharmaceuticals R&D, AstraZeneca","place":["Gothenburg, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Belfield","sequence":"additional","affiliation":[{"name":"Translational Genomics, Centre for Genomics Research, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca","place":["Gothenburg, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doriana","family":"Cellura","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton","place":["Southampton, United Kingdom"]},{"name":"NIHR Southampton Biomedical Research Centre, University Hospital Southampton","place":["Southampton, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damla","family":"Etal","sequence":"additional","affiliation":[{"name":"Translational Genomics, Centre for Genomics Research, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca","place":["Gothenburg, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria V.","family":"Humbert","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton","place":["Southampton, United Kingdom"]},{"name":"NIHR Southampton Biomedical Research Centre, University Hospital Southampton","place":["Southampton, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Freeman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton","place":["Southampton, United Kingdom"]},{"name":"NIHR Southampton Biomedical Research Centre, University Hospital Southampton","place":["Southampton, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Rydin","sequence":"additional","affiliation":[{"name":"Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, Biopharmaceuticals R&D, AstraZeneca","place":["Gothenburg, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris","family":"Ostridge","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton","place":["Southampton, United Kingdom"]},{"name":"Early Clinical Development, Respiratory and Immunology R&D Biopharmaceuticals, AstraZeneca","place":["Gothenburg, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Platt","sequence":"additional","affiliation":[{"name":"Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, Biopharmaceuticals R&D, AstraZeneca","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair","family":"Watson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton","place":["Southampton, United Kingdom"]},{"name":"NIHR Southampton Biomedical Research Centre, University Hospital Southampton","place":["Southampton, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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