{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:57:22Z","timestamp":1791385042949,"version":"4.3.3"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Hepatocellular carcinoma (HCC) is a leading cause of cancer\u2010related death that develops as a consequence of obesity, cirrhosis, and chronic hepatitis. However, the pathways along which these changes occur remain incompletely understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>In this study, we show that the deubiquitinase USP30 is abundant in HCCs that arise in mice maintained on high\u2010fat diets. IKK\u03b2 phosphorylated and stabilized USP30, which promoted USP30 to deubiquitinate ATP citrate lyase (ACLY) and fatty acid synthase (FASN). IKK\u03b2 also directly phosphorylated ACLY and facilitated the interaction between USP30 and ACLY and the latter\u2019s deubiquitination. In HCCs arising in DEN\/CCl<jats:sub>4<\/jats:sub>\u2010treated mice, USP30 deletion attenuated lipogenesis, inflammation, and tumorigenesis regardless of diet. The combination of ACLY inhibitor and programmed death ligand 1 antibody largely suppressed chemical\u2010induced hepatocarcinogenesis. The IKK\u03b2\u2010USP30\u2010ACLY axis was also found to be up\u2010regulated in human HCCs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This study identifies an IKK\u03b2\u2010USP30\u2010ACLY axis that plays an essential and wide\u2010spread role in tumor metabolism and may be a potential therapeutic target in HCC.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31249","type":"journal-article","created":{"date-parts":[[2020,3,28]],"date-time":"2020-03-28T02:03:41Z","timestamp":1585361021000},"page":"160-174","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":126,"title":["The IKK\u03b2\u2010USP30\u2010ACLY Axis Controls Lipogenesis and Tumorigenesis"],"prefix":"10.1097","volume":"73","author":[{"given":"Li","family":"Gu","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis,College of Life Sciences,Wuhan University,Wuhan,China"},{"name":"Frontier Science Center for Immunology and Metabolism,Medical Research Institute, Wuhan University,Wuhan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahui","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis,College of Life Sciences,Wuhan University,Wuhan,China"},{"name":"Frontier Science Center for Immunology and Metabolism,Medical Research Institute, Wuhan University,Wuhan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Lin","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis,College of Life Sciences,Wuhan University,Wuhan,China"},{"name":"Frontier Science Center for Immunology and Metabolism,Medical Research Institute, Wuhan University,Wuhan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjun","family":"Lu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis,College of Life Sciences,Wuhan University,Wuhan,China"},{"name":"Frontier Science Center for Immunology and Metabolism,Medical Research Institute, Wuhan University,Wuhan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis,College of Life Sciences,Wuhan University,Wuhan,China"},{"name":"Frontier Science Center for Immunology and Metabolism,Medical Research Institute, Wuhan University,Wuhan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Zhongnan Hospital of Wuhan University School of Medicine,Wuhan,China"},{"name":"Hubei Clinical Center and Key Laboratory for Intestinal and Colorectal 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