{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:00:17Z","timestamp":1785438017103,"version":"3.56.0"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Docetaxel (DTX) is widely used in lung cancer (LC), but its therapeutic efficacy is limited due to frequent development of chemoresistance. Epigenetic regulation via N6\u2010methyladenosine (m6A) has been implicated in tumor progression and drug resistance. The mechanisms underlying the biological resistance of methyltransferase\u2010like 14 (METTL14) and dickkopf 4 (DKK4) in LC remain incompletely understood. The expression levels of mRNA and protein of DKK4 and METTL14 were detected through RT\u2010qPCR and western blot analysis. DTX was administered to A549 and H1299 cells for the establishment of DTX\u2010resistant cell lines (A549\/DTX and H1299\/DTX). Half maximal inhibitory concentration (IC50) of A549\/DTX and H1299\/DTX cells was tested by Methylthiazolyldiphenyl\u2010tetrazolium bromide (MTT) assay. The detection of cell proliferation was carried out by EdU. Flow cytometry was utilized to analyze cell cycle, apoptosis, and M2 macrophage proportion. Transwell was employed to assess cell migration and invasion. The m6A level was measured using methylated RNA Immunoprecipitation (MeRIP) assay. A mouse xenograft model was established for the purpose of analysis in vivo. DKK4 and METTL14 were upregulated in LC and significantly increased in A549\/DTX and H1299\/DTX cells. The downregulation of DKK4 led to diminished proliferation, cell cycle arrest, increased apoptosis, decreased cell migration and invasion, and reduced proportion of M2 macrophages in A549\/DTX and H1299\/DTX cells. DKK4 enhanced DTX resistance in LC in vivo. METTL14 stimulated the m6A methylation of DKK4 mRNA. METTL14 facilitated the malignant growth of DTX\u2010resistant cells and the polarization of M2 macrophages by modulating DKK4 expression. METTL14 targeting DKK4 influenced LC progression and DTX resistance, indicating that METTL14 could serve as a potential therapeutic target to overcome DTX resistance in clinical settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70587","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:09:51Z","timestamp":1762762191000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["METTL14 Mediates Malignant Progression and Docetaxel Resistance of Lung Cancer by Regulating DKK4 Expression Through m6A Methylation Modification"],"prefix":"10.1002","volume":"39","author":[{"given":"Xueliang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Shanxi Province Cancer Hospital\/Shanxi Hospital Affiliated to Cancer Hospital Chinese Academy of Medical Sciences\/Cancer Hospital Affiliated to Shanxi Medical University Taiyuan City Shanxi 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