{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:05:06Z","timestamp":1784268306544,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Hepatocellular Carcinoma (HCC) is a matter of great global public health importance; however, its current therapeutic effectiveness is deemed inadequate, and the range of therapeutic targets is limited. This study aimed to explore the efficacy of Bosutinib (BOS) in HCC and the underlying molecular mechanism.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Bioinformatic analysis, machine learning, and online databases were used for screening targets and molecular docking studies. The mRNA level of mammalian polo\u2010like kinase 1 (\n PLK1<\/jats:italic>\n ) was identified via real\u2010time quantitative PCR. The protein expression of PLK1, PTK2, and USP9X was detected using western blot. Cell viability, apoptosis, and migration were evaluated by MTT, flow cytometry, and transwell assay. The angiogenesis capacity was determined using tube formation assay. The glucose consumption, lactate production, and ATP\/ADP ratios were analysed using commercial kits. CO\u2010IP assay was used to confirm the interaction between\n PLK1<\/jats:italic>\n and\n USP9X<\/jats:italic>\n . A mouse model was used for exploring BOS in\u00a0vivo. Immunochemistry was used to examine\n PLK1<\/jats:italic>\n and\n USP9X<\/jats:italic>\n expression in tumours.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n This study illustrated that BOS inhibited proliferation, migration, angiogenesis, and glycolysis of HCC cells. Bioinformatic analysis and machine learning identified\n PLK1<\/jats:italic>\n as a core gene related to the glycolysis of HCC.\n PLK1<\/jats:italic>\n was upregulated in HCC and correlated with an unfavourable prognosis. Further evaluation showed that the anti\u2010tumour effects of BOS were impaired by\n PLK1<\/jats:italic>\n overexpression. In addition, BOS treatment inhibited PLK1 protein level, while its mRNA level was not affected. Moreover, Bosutinib inhibited USP9X to reduce the deubiquitination of PLK1. CO\u2010IP assay indicated that reduced USP9X could enhance the ubiquitination of PLK1 and reduce protein stability. Finally, BOS showed anti\u2010tumour effects in a mouse model.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This study revealed that BOS inhibited cell proliferation, migration, angiogenesis, and glycolysis via suppressing\n USP9X<\/jats:italic>\n , thus reducing deubiquitination of\n PLK1<\/jats:italic>\n in HCC, demonstrating the potential of BOS for the treatment of HCC.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/1440-1681.70147","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T10:58:57Z","timestamp":1784113137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bosutinib Inhibits\n USP9X<\/i>\n to Suppress the Proliferation, Migration, Angiogenesis and Glycolysis of Hepatocellular Carcinoma Cells by Deubiquitinating\n 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