{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:25:46Z","timestamp":1786951546774,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Trichloroethylene (TCE), a pervasive environmental contaminant, is epidemiologically linked to kidney cancer, but the precise molecular mechanisms underlying this association remain insufficiently elucidated. To decipher the toxicological network, an integrated approach combining network toxicology, molecular docking, and in vitro validation was employed, resulting in the identification of TP53, ACTB, and CASP3 as pivotal hubs from 599 intersecting targets. Functional enrichment analyses implicated these targets in the dysregulation of cellular proliferation and apoptosis, predominantly mediated by the PI3K\u2010Akt signaling cascade, while clinical correlation analysis revealed that their significant overexpression in tumor tissues was associated with advanced pathological staging, unfavorable prognosis, and heightened infiltration of immunosuppressive cell populations, including Tr1 cells, macrophages, and exhausted T cells. Furthermore, potential binding interactions between TCE and these proteins were predicted by molecular docking and subsequently validated by in vitro experiments, wherein TCE exposure dose\u2010dependently upregulated TP53 and ACTB expression while concomitantly reducing cleaved CASP3 levels. Collectively, this study establishes a mechanistic framework demonstrating that TCE promotes kidney carcinogenesis by directly dysregulating TP53, ACTB, and CASP3, offering critical insights into environ\u2010mental oncogenesis and potential therapeutic interventions.<\/jats:p>","DOI":"10.1002\/jbt.71071","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T19:40:30Z","timestamp":1786563630000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elucidating the Mechanisms of Trichloroethylene\u2010Induced Kidney Cancer: Network Toxicology, Molecular Docking, and In Vitro Validation"],"prefix":"10.1002","volume":"40","author":[{"given":"Weijie","family":"Ma","sequence":"first","affiliation":[{"name":"Oncology Hematology Department Fengdu People's Hospital Chongqing 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