{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T10:49:27Z","timestamp":1791802167477,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"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":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study aims to investigate the biological function, molecular mechanisms, and impact on the tumor microenvironment of the ubiquitin\u2010conjugating enzyme E2S (UBE2S) in the progression of kidney renal clear cell carcinoma (KIRC). Based on the TCGA and GEPIA databases, the relationship between UBE2S expression and patient prognosis was analyzed. Overexpression and knockdown models of UBE2S were established in Caki\u20101 and 786\u2010O cell lines. Cell proliferation, apoptosis, and migration capabilities were assessed using CCK\u20108 assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay. Protein\u2010protein interactions and expression regulatory mechanisms were validated by co\u2010immunoprecipitation and Western blot. The proteasome inhibitor MG132 and ubiquitination assays were employed to investigate protein degradation mechanisms. Macrophage polarization was analyzed using a cell co\u2010culture system, immunofluorescence staining, and Western blot. UBE2S is highly expressed in KIRC tissues and is associated with poor patient prognosis. Functional experiments demonstrate that UBE2S promotes KIRC cell proliferation and migration while inhibiting apoptosis. Mechanistically, UBE2S directly binds to and positively regulates CDC20 protein expression, and its oncogenic functions depend on CDC20. Furthermore, knockdown of UBE2S induces cuproptosis by activating FDX1 protein, thereby enhancing cellular sensitivity to cuproptosis inducers. UBE2S promotes FDX1 protein degradation via the ubiquitin\u2010proteasome pathway. Additionally, tumor cells with high UBE2S expression promote macrophage polarization toward the M2 phenotype. UBE2S drives KIRC progression by regulating CDC20 expression and suppressing FDX1\u2010mediated cuproptosis, thereby promoting tumor\u2010associated macrophage polarization.<\/jats:p>","DOI":"10.1002\/mc.70171","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T18:39:54Z","timestamp":1788115194000},"page":"1495-1508","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["UBE2S Promotes KIRC Progression by Regulating CDC20 Expression and Suppressing FDX1\u2010Mediated Cuproptosis, While Promoting M2 Macrophage Polarization"],"prefix":"10.1002","volume":"65","author":[{"given":"Junru","family":"Chen","sequence":"first","affiliation":[{"name":"Urology Department People's Hospital of Ningxia Hui Autonomous Region Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Gao","sequence":"additional","affiliation":[{"name":"Urology Department General Hospital of Ningxia Medical University Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelong","family":"Feng","sequence":"additional","affiliation":[{"name":"Urology Department People's Hospital of Ningxia Hui Autonomous Region Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Urology Department People's Hospital of Ningxia Hui Autonomous Region Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Jia","sequence":"additional","affiliation":[{"name":"Urology Department People's Hospital of Ningxia Hui Autonomous Region Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Anesthesia Surgery Department People's Hospital of Ningxia Hui Autonomous Region Yinchuan 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