{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T06:45:15Z","timestamp":1782715515983,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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 Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>To investigate the interplay between ubiquitin\u2010specific protease 21 (USP21) and programmed death\u2010ligand 1 (PD\u2010L1) in the context of Transarterial chemoembolisation (TACE) treatment for hepatocellular carcinoma (HCC) and explore a novel combinatorial strategy to enhance therapeutic efficacy. USP21 was silenced in HCC cells and in two distinct mouse models: a diethylnitrosamine (DEN)\u2010induced orthotopic HCC model and a HepG2 subcutaneous xenograft model. The effects of USP21 knockdown, TACE and their combination on tumour growth, proliferation, invasion and apoptosis were evaluated. The regulation of PD\u2010L1 by USP21 was studied through co\u2010immunoprecipitation and deubiquitination assays. Rescue experiments were performed by overexpressing PD\u2010L1. Silencing USP21 attenuated HCC cell proliferation and invasion. Combining TACE with USP21 knockdown significantly enhanced antitumour effects compared to monotherapies. USP21 interacted with and deubiquitinated PD\u2010L1, stabilising its expression. Cycloheximide chase assays with densitometric quantification demonstrated that USP21 significantly prolonged the half\u2010life of PD\u2010L1 protein. Overexpression of PD\u2010L1 reversed the inhibitory effects of USP21 silencing and the enhanced therapeutic efficacy of the TACE\/USP21 knockdown combination. USP21 stabilises PD\u2010L1 through deubiquitination, promoting HCC progression and immune evasion. Silencing USP21 enhances the therapeutic efficacy of TACE by modulating PD\u2010L1 expression, suggesting a promising combinatorial strategy for HCC treatment.<\/jats:p>","DOI":"10.1111\/jcmm.71209","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:17:08Z","timestamp":1781583428000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combining Transarterial Chemoembolisation With Reduced Deubiquitinase Activity Reduces Hepatocellular Carcinoma Progression"],"prefix":"10.1111","volume":"30","author":[{"given":"Yun","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Intervention The Affiliated Hospital of Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Intervention The Affiliated Hospital of Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenge","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Intervention The Affiliated Hospital of Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Intervention The Affiliated Hospital of Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0483-6800","authenticated-orcid":false,"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Intervention The Affiliated Hospital of Jiangnan University  Wuxi 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