{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:51:18Z","timestamp":1789487478483,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"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":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    As a key regulator of\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    \u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) modification, methyltransferase\u2010like 14 (METTL14) has been implicated in the progression of various cancers; however, its functional role in breast cancer remains controversial. Isorhapontigenin (ISO), a natural polyphenolic compound, has been identified as a METTL14 agonist with antitumor potential in multiple malignancies. Nevertheless, the biological function of ISO in breast cancer, particularly its mechanism of regulating METTL14 and downstream signaling pathways, has not been fully elucidated. This study aimed to explore the effects of ISO on breast cancer cell viability, colony\u2010forming efficiency, and ferroptosis and investigate whether ISO exerts these effects by regulating METTL14 expression. Bioinformatics analyses were performed to identify differentially expressed m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010related genes in breast cancer tissues. CCK\u20108 and colony formation assays were used to evaluate the effects of ISO on breast cancer cell viability and colony\u2010forming efficiency. Ferroptosis was assessed by quantifying ferroptosis\u2010related indicators, including reactive oxygen species, glutathione, malondialdehyde, and intracellular Fe\n                    <jats:sup>2+<\/jats:sup>\n                    levels. METTL14\u2010overexpressing cell lines, as well as METTL14\u2010 and SLC7A11\u2010silenced cell lines, were constructed to explore gene functions. Bioinformatics analysis revealed that METTL14 is downregulated in basal\u2010like and HER2\u2010enriched breast cancer subtypes, and METTL14 overexpression suppressed cell viability and colony\u2010forming efficiency and promoted ferroptosis in these METTL14\u2010low subtypes. ISO also suppressed cell viability and colony\u2010forming efficiency and induced ferroptosis in these cell subtypes. Mechanistically, ISO exerted its effects by upregulating METTL14 expression, which in turn induced m\n                    <jats:sup>6<\/jats:sup>\n                    A modification of\n                    <jats:italic>SLC7A11<\/jats:italic>\n                    mRNA. In conclusion, ISO reduced cell viability and colony\u2010forming efficiency, and promoted ferroptosis in HER2\u2010enriched and basal\u2010like breast cancer cells through promoting METTL14\u2010dependent m\n                    <jats:sup>6<\/jats:sup>\n                    A modification of\n                    <jats:italic>SLC7A11<\/jats:italic>\n                    mRNA. These findings suggest that ISO may serve as a candidate therapeutic agent for the treatment of HER2\u2010enriched and basal\u2010like breast cancer.\n                  <\/jats:p>","DOI":"10.1002\/mc.70153","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:21:30Z","timestamp":1784809290000},"page":"1194-1208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Isorhapontigenin on Cell Viability, Colony\u2010Forming Efficiency, and Ferroptosis via Methyltransferase\u2010Like 14\u2010Mediated m\n                    <sup>6<\/sup>\n                    A Modification of Solute Carrier Family 7 Member 11 in Human Epidermal Growth Factor Receptor 2\u2010Enriched and Basal\u2010Like Breast Cancer"],"prefix":"10.1002","volume":"65","author":[{"given":"Zhong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Thyroid and Breast Surgery Nanyang First People's Hospital Nanyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongji","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery Nanyang First People's Hospital Nanyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Thyroid, Breast, and Hernia Surgery Tiantai People's Hospital of Zhejiang Province Taizhou 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