{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:01:06Z","timestamp":1785391266996,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Triple negative breast cancer (TNBC) is the most malignant type of breast cancer, and its treatment usually uses paclitaxel for chemotherapy. However, TNBC cells are increasingly resistant to paclitaxel. In the context of paclitaxel resistance, we investigated the role of DNA methylation and the DNA methyltransferase DNMT3B methylation regulatory proteins, as well as their interaction with ferroptosis regulator SLC25A6, in regulating paclitaxel resistance and ferroptosis in TNBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used database integration analysis methods, combined with bioinformatics screening,\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      cell and animal experimental models to analyze DNA methylation and the effect of DNMT3B on SLC25A6 DNA methylation. We explored the effects of the DNMT3B-SLC25A6 regulatory axis on ferroptosis and paclitaxel resistance using electron microscopy, fluorescent probes, and detection of key biomarkers. Statistical significance was evaluated using Student\u2019s t-test and analysis of variance (ANOVA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DNMT3B was significantly overexpressed in paclitaxel-resistant TNBC tissues and cell lines, correlating with enhanced proliferation, migration, and ferroptosis. Mechanistically, DNMT3B induced DNA methylation of SLC25A6 through its 252-bp CpG island, inhibited its protein expression, and triggered ferroptosis by disrupting mitochondrial function and redox balance, leading to paclitaxel resistance in TNBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In paclitaxel-resistant TNBC, DNMT3B regulates SLC25A6 expression via DNA methylation, and the DNMT3B-SLC25A6 regulatory axis acts as a central regulator of ferroptosis, promoting paclitaxel resistance in TNBC by suppressing ferroptosis via oxidative stress imbalance. These findings provide promising therapeutic targets for the intervention of TNBC paclitaxel resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1887314","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:39:15Z","timestamp":1785389955000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["DNMT3B- SLC25A6 axis-mediated DNA methylation regulates ferroptosis to promote paclitaxel resistance in triple-negative breast cancer"],"prefix":"10.3389","volume":"14","author":[{"given":"Hao","family":"Wu","sequence":"first","affiliation":[{"name":"Department of General Surgery, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Breast Center, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Breast Center, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Breast Center, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenggui","family":"Du","sequence":"additional","affiliation":[{"name":"Department of General Surgery, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Breast Center, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"B2","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s41571-021-00565-2","article-title":"Treatment landscape of triple-negative breast cancer - expanded options, evolving needs","volume":"19","author":"Bianchini","year":"2022","journal-title":"Nat. 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