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However, the precise function of DCAF7 in regulating the progression of hepatocellular carcinoma (HCC) ferroptosis remains elusive. In this study, we demonstrate that DCAF7 and the deubiquitinase USP2 are highly expressed in HCC. Genetic ablation of\n                    <jats:italic>DCAF7<\/jats:italic>\n                    or pharmacological inhibition of USP2 sensitizes HCC to ferroptosis and inhibits HCC progression both in vitro and in vivo. Mechanistically, DCAF7 recruits USP2 to inhibit clockophagy (the selective autophagic degradation of core clock protein BMAL1 mediated through p62\/SQSTM1) by reducing BMAL1 K63-linked polyubiquitination. Targeting either DCAF7 or USP2 triggers clockophagy-induced ferroptosis through the HIF1\u03b1-SLC7A11 axis in HCC cells. Collectively, our study establishes DCAF7 and USP2 as novel suppressors of clockophagy-induced ferroptosis and reveals the potential therapeutic targets for HCC treatment.\n                  <\/jats:p>","DOI":"10.1038\/s41419-025-07977-3","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T17:10:42Z","timestamp":1756401042000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["DCAF7 recruits USP2 to facilitate hepatocellular carcinoma progression by suppressing clockophagy-induced ferroptosis"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2853-2477","authenticated-orcid":false,"given":"Honglv","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-1335","authenticated-orcid":false,"given":"Li","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darran P.","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-1266","authenticated-orcid":false,"given":"Jingjing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4753-4769","authenticated-orcid":false,"given":"Guoqiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"7977_CR1","doi-asserted-by":"publisher","first-page":"2226","DOI":"10.1158\/0008-5472.CAN-22-3599","volume":"83","author":"J Xu","year":"2023","unstructured":"Xu J, Ye Z, Zhuo Q, Gao H, Qin Y, Lou X, et al. 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