{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:09:59Z","timestamp":1788844199567,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"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":["Asia-Pac J Clncl Oncology"],"abstract":"ABSTRACT<\/jats:title>\n \n Triple\u2010negative breast cancer (TNBC) is an aggressive malignancy with limited treatment options, highlighting the urgent need to identify novel therapeutic targets. The present study investigates the role of the RNA methyltransferase METTL3 in promoting TNBC progression by modulating a ferroptosis\u2010related phenotype, an iron\u2010dependent form of regulated cell death. Using TNBC cell lines (BT549 and MDA\u2010MB\u2010231), we demonstrated that METTL3 overexpression significantly enhanced cell proliferation, while its knockdown suppressed growth. Mechanistically, METTL3 was associated with decreased lipid peroxidation, reactive oxygen species (ROS), intracellular Fe\n 2<\/jats:sup>\n +<\/jats:sup>\n levels, and the pro\u2010ferroptotic protein ACSL4, alongside increased glutathione and the key ferroptosis inhibitor GPX4. Bioinformatic analysis, MeRIP\u2010PCR, and actinomycin D chase assays indicated that METTL3 was associated with increased N\n 6<\/jats:sup>\n \u2010methyladenosine (m6A) enrichment, expression, and persistence of ELF1 mRNA. Dual\u2010luciferase reporter assay further suggested that ELF1 may be involved in GPX4 transcriptional regulation. Crucially, the pro\u2010proliferative and ferroptosis\u2010associated effects of METTL3 overexpression were partially attenuated upon ELF1 knockdown or treatment with the ferroptosis inducer erastin. In conclusion, our findings suggest a novel METTL3\/ELF1\/GPX4 axis through which METTL3 promotes TNBC growth by regulating oxidative stress and ferroptosis\u2010related markers, providing a basis for further investigation of this pathway in the context of TNBC biology and therapeutic development.\n <\/jats:p>","DOI":"10.1111\/ajco.70171","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:23:28Z","timestamp":1788841408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["METTL3 Promotes the Growth of Triple\u2010Negative Breast Cancer Cells by Modulating Ferroptosis\u2010Related Oxidative Stress via the ELF1\/GPX4 Axis"],"prefix":"10.1111","author":[{"given":"Jincheng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oncology Surgery(General Surgery Clinical Medical Center) The Second Affiliated Hospital of Bengbu Medical University, Huaishang District Bengbu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery(General Surgery Clinical Medical Center) The Second Affiliated Hospital of Bengbu Medical University, Huaishang District Bengbu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy The Second Affiliated Hospital of Bengbu Medical University, Huaishang District Bengbu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery(General Surgery Clinical Medical Center) The Second Affiliated Hospital of Bengbu Medical University, Huaishang District Bengbu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery(General Surgery Clinical Medical Center) The Second Affiliated Hospital of Bengbu Medical University, Huaishang District Bengbu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery(General Surgery Clinical Medical Center) The Second Affiliated Hospital of Bengbu Medical University, Huaishang District Bengbu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery(General Surgery Clinical Medical Center) The Second Affiliated Hospital of Bengbu Medical University, Huaishang District Bengbu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohu","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery(General Surgery Clinical Medical Center) The Second Affiliated Hospital of Bengbu Medical University, Huaishang District Bengbu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiguang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery(General Surgery Clinical Medical Center) The Second Affiliated Hospital of Bengbu Medical University, Huaishang District Bengbu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguang","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Oncology Surgery(General Surgery Clinical Medical Center) The Second Affiliated Hospital of Bengbu Medical University, Huaishang District Bengbu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"issue":"20","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"5898","DOI":"10.1039\/D4TB02701A","article-title":"Zwitterionic Polymer\u2010Coated Magnetic Nanoparticle Induced Chemotherapy and Ferroptosis for Triple\u2010Negative Breast Cancer Therapy","volume":"13","author":"Zhang J.","year":"2025","journal-title":"Journal of Materials Chemistry B"},{"issue":"17","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"8757","DOI":"10.7150\/thno.116013","article-title":"Injectable SF\u2010Platform Orchestrates GPX4\u2010Targeted Ferroptosis\u2010Autophagy\u2010Immunogenic Circuit for Overcoming Oxidative Resistance in Triple\u2010Negative Breast Cancer","volume":"15","author":"Yuan H.","year":"2025","journal-title":"Theranostics"},{"issue":"8","key":"e_1_2_10_4_1","first-page":"1","article-title":"TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough","volume":"9","author":"Singh D. D.","year":"2021","journal-title":"Nanomedicine, and Immunotherapy Biomedicines"},{"issue":"1","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cmet.2022.09.021","article-title":"Ferroptosis Heterogeneity in Triple\u2010Negative Breast Cancer Reveals an Innovative Immunotherapy Combination Strategy","volume":"35","author":"Yang F.","year":"2023","journal-title":"Cell Metabolism"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.2147\/CMAR.S503932","article-title":"Iron\u2010dependent cell death: Exploring ferroptosis as a unique target in triple\u2010negative breast cancer management","volume":"17","author":"Tan L.\u2010K.","year":"2025","journal-title":"Cancer Management and Research"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.jare.2024.09.027","article-title":"Salidroside Sensitizes Triple\u2010Negative Breast Cancer to Ferroptosis by SCD1\u2010Mediated Lipogenesis and NCOA4\u2010Mediated Ferritinophagy","volume":"74","author":"Huang G.","year":"2025","journal-title":"Journal of Advanced Research"},{"issue":"1","key":"e_1_2_10_8_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.xcrm.2024.101915","article-title":"Dual Ferroptosis Induction in N2\u2010TANs and TNBC Cells via FTH1 Targeting: A Therapeutic Strategy for Triple\u2010Negative Breast Cancer","volume":"6","author":"Liu Y.","year":"2025","journal-title":"Cell Reports Medicine"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbrc.2025.152389","article-title":"Identification of Small Compounds Targeting Ferroptosis in Triple\u2010Negative Breast Cancer by Using an Integrated Computational Approach","volume":"778","author":"Qin M.","year":"2025","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.tice.2024.102690","article-title":"METTL3\/IGF2BP1 Promotes the Development of Triple\u2010Negative Breast Cancer by Mediating m6A Methylation Modification of PRMT7","volume":"93","author":"Lu W.","year":"2025","journal-title":"Tissue and Cell"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.prp.2025.155865","article-title":"METTL3 Enhances Esophageal Squamous Cell Carcinoma Progression by Suppressing Ferroptosis Through the PBX3\/CA9 Cascade","volume":"269","author":"Yang L.","year":"2025","journal-title":"Pathology \u2013 Research and Practice"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2025.112024","article-title":"Gambogic Acid Induces Ferroptosis and Suppresses Colorectal Cancer Progression by Modulating the m6A Modification of p62","volume":"135","author":"Wang J.","year":"2025","journal-title":"Cellular Signaling"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2025.157257","article-title":"Eriocalyxin B Induces Ferroptosis Through SIRT3 Inhibition in Triple\u2010Negative Breast Cancer","volume":"148","author":"Chen X.","year":"2025","journal-title":"Phytomedicine"},{"issue":"7","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1080\/1120009X.2024.2421700","article-title":"METTL3\u2010Mediated m6A Modification Promotes Chemoresistance of Intrahepatic Cholangiocarcinoma by Up\u2010Regulating NRF2 to Inhibit Ferroptosis in Cisplatin\u2010Resistant Cells","volume":"37","author":"Zheng X.","year":"2025","journal-title":"Journal of Chemotherapy"},{"issue":"4","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s10735-025-10496-2","article-title":"METTL14 Induces Ferroptosis to Inhibit Colorectal Cancer Progression by Inhibiting TRIB3 via an m6A\u2010YTHDF2\u2010Dependent Manner","volume":"56","author":"Zhang D.","year":"2025","journal-title":"Journal of Molecular Histology"},{"issue":"1","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41420-025-02515-8","article-title":"ELF1\u2010Mediated Transactivation of METTL3\/YTHDF2 Promotes Nucleus Pulposus Cell Senescence via m6A\u2010Dependent Destabilization of E2F3 mRNA in Intervertebral Disc Degeneration","volume":"11","author":"Liu X.\u2010W.","year":"2025","journal-title":"Cell Death Discovery"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2025.111649","article-title":"Mechanistic Study of METTL3 Inducing Ferroptosis to Promote Cervical Cancer Progression Through Mediating m6A Modification of COTE\u20101","volume":"128","author":"Min L.","year":"2025","journal-title":"Cellular Signalling"},{"issue":"12","key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/s41419-024-07274-5","article-title":"Overexpression of ELF3 in the PTEN\u2010Deficient Lung Epithelium Promotes Lung Cancer Development by Inhibiting Ferroptosis","volume":"15","author":"Yuan Z.","year":"2024","journal-title":"Cell Death and Disease"},{"issue":"1","key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1186\/s12951-021-01058-1","article-title":"Simvastatin Induced Ferroptosis for Triple\u2010Negative Breast Cancer Therapy","volume":"19","author":"Yao X.","year":"2021","journal-title":"Journal of Nanobiotechnology"},{"issue":"7","key":"e_1_2_10_20_1","doi-asserted-by":"crossref","DOI":"10.1111\/jcmm.18212","article-title":"SBFI26 Induces Triple\u2010Negative Breast Cancer Cells Ferroptosis via Lipid Peroxidation","volume":"28","author":"He G.","year":"2024","journal-title":"Journal of Cellular and Molecular Medicine"},{"issue":"1","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s43556-024-00208-9","article-title":"HJURP Sustains Ferroptosis Sensitivity of TNBC by Interacting With SLC7A11 and Maintaining Its Function","volume":"5","author":"Chen Y.","year":"2024","journal-title":"Molecular Biomedicine"},{"key":"e_1_2_10_22_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.tice.2025.102902","article-title":"METTL3\u2010Mediated m6A Modification of MT1G Inhibits Papillary Thyroid Carcinoma Cell Growth and Metastasis via Wnt\/\u03b2\u2010Catenin Pathway","volume":"95","author":"Liu J.","year":"2025","journal-title":"Tissue and Cell"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2025.177785","article-title":"METTL3\u2010Driven m6A Modifications in Esophageal Squamous Cell Carcinoma: Emerging Mechanisms, Biomarker Potential, and Therapeutic Innovations","volume":"1002","author":"Chun H.","year":"2025","journal-title":"European Journal of Pharmacology"}],"container-title":["Asia-Pacific Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ajco.70171","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ajco.70171","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ajco.70171","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:23:31Z","timestamp":1788841411000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ajco.70171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":22,"alternative-id":["10.1111\/ajco.70171"],"URL":"https:\/\/doi.org\/10.1111\/ajco.70171","archive":["Portico"],"relation":{},"ISSN":["1743-7555","1743-7563"],"issn-type":[{"value":"1743-7555","type":"print"},{"value":"1743-7563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"assertion":[{"value":"2025-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajco.70171"}}