{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:31:35Z","timestamp":1787923895425,"version":"build-2784847793"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2024AAC05063"],"award-info":[{"award-number":["2024AAC05063"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013494","name":"West Light Foundation, Chinese Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013494","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Per- and polyfluoroalkyl substances (PFAS) are omnipresent, persistent contaminants associated with rising ovarian cancer incidence; however, the molecular circuitry linking PFAS to ovarian tumorigenesis remains obscure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, an integrated network toxicology\u2013molecular docking pipeline was developed to interrogate ten environmentally abundant PFAS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Comprehensive interactome mapping identified 1,042 PFAS\u2013protein interactions that converge on eight transcriptional hubs (HDAC1, SIRT1, ESR1, RXRA, PTGS2, MMP9, HDAC2 and HDAC3), subsequently validated as significantly overexpressed in ovarian tumours versus normal tissue pathway enrichment indicated that these mediators synchronize epigenetic silencing, estrogen signalling, inflammatory prostaglandin synthesis and extracellular-matrix remodelling, thereby may coordinate processes potentially associated with PFAS-associated initiation and progression. Competitive docking further showed that long-chain PFOS and PFOA are predicted the strongest binding affinities to the catalytic domains of HDACs 1\u20133, mechanistically explaining the observed transcriptomic alterations. Human ovarian granulosa-like tumor cell line (KGN) was exposed to PFOA, which works as a representative PFAS compound, showed a significant increase of cell proliferation and migration, leading to an alteration of gene expression previously identified by network toxicology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings provides a systems-level predictive framework for understanding PFAS-associated ovarian oncogenesis, furnish quantitative biomarkers for exposure\u2013response modelling, and prioritize HDAC inhibition as prioritized candidate mediators to mitigate PFAS-related cancer risk with immediate translational implications for public-health protection and regulatory guideline revision.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1905013","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:53:26Z","timestamp":1787921606000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative network toxicology and molecular docking reveal epigenetic and endocrine-disrupting mechanisms of PFAS in ovarian cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Yulu","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Ding","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanjie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University","place":["Yinchuan, China"]},{"name":"The First Clinical Medical College, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University","place":["Yinchuan, China"]},{"name":"Shengzhou Food and Drug Testing Center","place":["Shaoxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhou","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengge","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyi","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University","place":["Yinchuan, China"]},{"name":"Reproductive Medicine Center, The First Clinical Medical College, Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"972","DOI":"10.6004\/jnccn.2022.0047","article-title":"NCCN guidelines\u00ae insights: ovarian cancer, version 3.2022","volume":"20","author":"Armstrong","year":"2022","journal-title":"J. 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