{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:20:24Z","timestamp":1784823624422,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osimertinib (OSI) resistance in non\u2010small cell lung cancer (NSCLC) remains a significant challenge. This report explored the precise role of USP28 on OSI resistance in NSCLC and identified a functional downstream effector. OSI\u2010resistant H1975 cells (H1975\/OSI) were established by long\u2010term OSI exposure. USP28 and SIRT1 expression levels were analyzed by quantitative PCR, immunoblotting, and immunohistochemistry. Functional assays included cell viability, colony formation, EdU incorporation, apoptosis analysis, and glycolysis assays. The interaction between USP28 and SIRT1 was confirmed by co\u2010immunoprecipitation (Co\u2010IP) assay and SIRT1 protein stability analysis. In\u00a0vivo validation was performed using H1975\/OSI xenograft models. USP28 and SIRT1 were upregulated in H1975\/OSI cells and OSI\u2010resistant NSCLC tissues. USP28 overexpression enhanced cell proliferation and glycolysis, suppressed apoptosis, and conferred OSI resistance in H1975 cells, while its depletion exerted opposite effects in H1975\/OSI cells. Mechanistically, USP28 stabilized SIRT1 by deubiquitination. SIRT1 knockdown attenuated the effects of USP28 overexpression, while SIRT1 restoration reversed the phenotype alterations upon USP28 depletion. In\u00a0vivo, USP28 depletion sensitized H1975\/OSI xenografts to OSI treatment. Our study indicates that USP28 promotes OSI resistance in NSCLC by deubiquitinating SIRT1. Targeting the USP28\/SIRT1 axis may represent a novel therapeutic approach to overcome OSI resistance in EGFR\u2010mutant NSCLC.<\/jats:p>","DOI":"10.1002\/kjm2.70095","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T07:07:35Z","timestamp":1756192055000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>USP28<\/scp>\n                    Promotes Osimertinib Resistance in\n                    <scp>H1975 NSCLC<\/scp>\n                    Cells by Deubiquitinating and Stabilizing\n                    <scp>SIRT1<\/scp>"],"prefix":"10.1002","volume":"42","author":[{"given":"Hu\u2010Sen","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Weifang People's Hospital  Weifang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu\u2010Mei","family":"Li","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Medical 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