{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:35:26Z","timestamp":1793205326478,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"60","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ferroptosis can be therapeutically induced through GPX4 inhibition, but the mechanisms that determine ferroptosis sensitivity in prostate cancer remain incompletely understood. Here, we combined genome\u2010wide CRISPR screening under graded GPX4 inhibition with mechanistic perturbation\u2013rescue experiments and validation in xenograft and immunocompetent syngeneic prostate cancer models. We identified MEPCE loss as a conserved sensitizer to ferroptosis. Mechanistically, MEPCE depletion destabilized RN7SK and disrupted the HEXIM1\u2013P\u2010TEFb complex, consistent with CDK9 release and enhanced RNA polymerase II Ser2 phosphorylation, thereby promoting transcriptional elongation. This state accelerated activation of a NRF2\/ARE stress program encompassing antioxidant defense and iron mobilization. Within this program, HMOX1 emerged as a kinetically sensitive effector whose rapid induction promoted labile iron accumulation and lipid peroxidation under GPX4 inhibition. In vivo, MEPCE suppression impaired tumor growth, enhanced the antitumor efficacy of ferroptosis induction, and was associated with pharmacodynamic markers of ferroptosis that were partially reversed by ferroptosis\u2010 or iron\u2010targeted rescue. Together, these findings identify a transcriptional pause\u2010control mechanism that links elongation dynamics to ferroptosis susceptibility and nominate the MEPCE\u2013RN7SK\u2013P\u2010TEFb axis as a potential therapeutic target for sensitizing prostate cancer to ferroptosis.<\/jats:p>","DOI":"10.1002\/advs.76958","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:04:29Z","timestamp":1785935069000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mepce Restrains Ferroptosis in Prostate Cancer Through 7SK\u2013P\u2010TEFb Pause Control"],"prefix":"10.1002","volume":"13","author":[{"given":"Tongtong","family":"Zhang","sequence":"first","affiliation":[{"name":"Urology Centre Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Surgical Institute of Integrative Medicine Shuguang Hospital Affiliated to Shanghai University 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