{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:37:27Z","timestamp":1793320647864,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Enhancing sensitivity to sorafenib can significantly extend the duration of resistance to it, offering substantial benefits for treating patients with hepatocellular carcinoma (HCC). However, the role of ferroptosis in influencing sorafenib sensitivity within HCC remains pivotal. The enhancer of zeste homolog 2 (EZH2) plays a significant role in promoting malignant progression in HCC, yet the relationship between ferroptosis, sorafenib sensitivity, and EZH2 is not entirely clear. Bioinformatic analysis indicates elevated EZH2 expression in HCC, predicting an unfavorable prognosis. Overexpressing EZH2 can drive HCC cell proliferation while simultaneously reducing ferroptosis. Further analysis reveals that EZH2 amplifies the modification of H3K27 me3, thereby influencing TFR2 expression. This results in decreased RNA polymerase II binding within the TFR2 promoter region, leading to reduced TFR2 expression. Knocking down EZH2 amplifies sorafenib sensitivity in HCC cells. In sorafenib\u2010resistant HepG2(HepG2\u2010SR) cells, the expression of EZH2 is increased. Moreover, combining tazemetostat\u2014an EZH2 inhibitor\u2014with sorafenib demonstrates significant synergistic ferroptosis\u2010promoting effects in HepG2\u2010SR cells. In conclusion, our study illustrates how EZH2 epigenetically regulates TFR2 expression through H3K27 me3, thereby suppressing ferroptosis. The combination of the tazemetostat with sorafenib exhibits superior synergistic effects in anticancer therapy and sensitizes the HepG2\u2010SR cells to sorafenib, shedding new light on delaying and ameliorating sorafenib resistance.<\/jats:p>","DOI":"10.1111\/cas.16186","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T06:46:06Z","timestamp":1713249966000},"page":"2220-2234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["<scp>EZH2<\/scp>\n                    suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of\n                    <scp>TFR2<\/scp>"],"prefix":"10.1111","volume":"115","author":[{"given":"Yongwei","family":"Lai","sequence":"first","affiliation":[{"name":"Key Laboratory of Microecology\u2010Immune Regulatory Network and Related Diseases School of Basic Medicine Jiamusi University  Jiamusi 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