{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T05:16:09Z","timestamp":1766639769119,"version":"3.48.0"},"reference-count":124,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["HL134610"],"award-info":[{"award-number":["HL134610"]}]},{"name":"NIH","award":["HL146369"],"award-info":[{"award-number":["HL146369"]}]},{"name":"NIH","award":["UG3HG013615"],"award-info":[{"award-number":["UG3HG013615"]}]},{"name":"BHSF-FIU pilot project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>N6-methyladenosine (m6A) represents the most abundant and tightly controlled modification within eukaryotic mRNA, critically influencing RNA metabolism and function. The m6A methyltransferase Like-3 (METTL3), responsible for the complex\u2019s catalytic function, has emerged as a central epitranscriptomic regulator governing mRNA stability, alternative splicing, nuclear export, and the efficiency of mRNA translation. Converging research shows that METTL3 is involved in the pathogenesis of numerous disorders via m6A-dependent, post-transcriptional regulation of gene programs controlling cell growth, migration, and immune pathways. Regarding pulmonary pathophysiology, METTL3-mediated m6A is tied to disease initiation and progression in conditions such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), lung infections, acute respiratory distress syndrome (ARDS). This review summarizes the contemporary evidence for METTL3\u2019s roles and regulatory network in diverse pulmonary pathologies. We further highlight emerging strategies for targeting METTL3 as a potential therapeutic approach, underscoring its promise as a novel epitranscriptomic target. Beyond inflammatory and fibrotic disorders, we also summarize emerging evidence linking METTL3 to lung cancer and briefly outline other respiratory conditions (e.g., ILD, bronchiectasis, and secondary pulmonary hypertension), highlighting common translational themes and remaining gaps. Further studies are required to clarify the disease-specific and context-dependent actions of METTL3 and to advance the clinical translation of m6A-based therapies.<\/jats:p>","DOI":"10.3390\/ijms27010085","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T16:41:19Z","timestamp":1766594479000},"page":"85","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Emerging Role of METTL3 in Lung Diseases"],"prefix":"10.3390","volume":"27","author":[{"given":"Yishu","family":"Dong","sequence":"first","affiliation":[{"name":"Center of Translational Science, Florida International University, Port St. Lucie, FL 34990, USA"},{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1875-8293","authenticated-orcid":false,"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Translational Science, Florida International University, Port St. Lucie, FL 34990, USA"},{"name":"Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8868-2138","authenticated-orcid":false,"given":"David","family":"Marciano","sequence":"additional","affiliation":[{"name":"Center of Translational Science, Florida International University, Port St. Lucie, FL 34990, USA"},{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0155-5887","authenticated-orcid":false,"given":"Adel","family":"Nefzi","sequence":"additional","affiliation":[{"name":"Center of Translational Science, Florida International University, Port St. Lucie, FL 34990, USA"},{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M.","family":"Black","sequence":"additional","affiliation":[{"name":"Center of Translational Science, Florida International University, Port St. Lucie, FL 34990, USA"},{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"},{"name":"Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Translational Science, Florida International University, Port St. Lucie, FL 34990, USA"},{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"},{"name":"Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1126\/science.aau1646","article-title":"RNA modifications modulate gene expression during development","volume":"361","author":"Frye","year":"2018","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41576-020-00295-8","article-title":"The epitranscriptome beyond m6A","volume":"22","author":"Wiener","year":"2021","journal-title":"Nat. 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