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Bisphenols contribute to carcinogenesis due to their endocrine-disrupting properties, particularly in breast cancer. However, the relationship between BPs exposure and putative cancer risk, as well as the underlying molecular mechanisms, remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study employed network toxicology, molecular docking, molecular dynamics simulation, machine learning, and bioinformatics to systematically investigate the molecular mechanisms and potential targets associated with carcinogenic risks of five BPs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The findings revealed that BPs exposure increases cancer risk by targeting 26 core proteins, including RXRA, AKT2, and CYCS, leading to oxidative stress and modulation of cancer-related signaling pathways such as MAPK, PI3K\/AKT, Ras, and VEGF. Molecular docking and dynamics simulations demonstrated stable binding interactions between RXRA and all five BPs. Analysis of the TCM database indicated that\n                      <jats:italic>Ginseng<\/jats:italic>\n                      ,\n                      <jats:italic>Turmeric<\/jats:italic>\n                      , and\n                      <jats:italic>Salvia miltiorrhiza<\/jats:italic>\n                      can mitigate BPs-induced cancer risk by targeting these core proteins. Pan-cancer analysis showed that kidney renal clear cell carcinoma (KIRC) and low-grade glioma (LGG) are most strongly associated with BPs exposure. Diagnostic and prognostic models based on core targets exhibited high predictive accuracy, offering valuable clinical decision support. Single-cell sequencing revealed that core targets are primarily localized in immune cells in KIRC and glioma cells in LGG.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides a theoretical foundation for evaluating cancer risk associated with BPs exposure and establishes a novel framework for understanding the pathogenesis and potential therapeutic strategies for environmental pollutants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40246-026-00948-5","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T06:05:05Z","timestamp":1773468305000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unraveling the potential carcinogenic risk of bisphenols: a comprehensive network analysis and computational toxicology insights"],"prefix":"10.1186","volume":"20","author":[{"given":"Tiegang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufang","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silin","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengni","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"948_CR1","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.enceco.2025.04.001","volume":"7","author":"Y Tang","year":"2025","unstructured":"Tang Y, Qin G, Qian N, Zeng X, Li R. 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