{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T03:17:07Z","timestamp":1775099827661,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The objective of this study was to investigate the expression levels and biological significance of <jats:italic>CKS2<\/jats:italic> in Burkitt cell lymphoma (BL) and diffuse large B\u2010cell lymphoma (DLBCL). Additionally, the potential synergistic anti\u2010tumor effects of <jats:italic>CKS2<\/jats:italic> knockdown in combination with etoposide in BL and DLBCL were explored for the first time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bioinformatics analysis was utilized to explore the transcriptional levels, prognostic value, and gene function enrichment of <jats:italic>CKS2<\/jats:italic> in BL and DLBCL. Specific shRNA sequences were designed to target <jats:italic>CKS2<\/jats:italic> for the purpose of constructing a lentiviral expression vector, and therapeutic effects were assessed through analyses of cell proliferation, cell cycle distribution, and cell apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>First, the study examined the increased transcriptional and protein levels of <jats:italic>CKS2<\/jats:italic> in BL and DLBCL through analysis of various databases and immunohistochemistry tests. Elevated <jats:italic>CKS2<\/jats:italic> expression was found to be correlated with a worse prognosis in BL and DLBCL patients, as evidenced by data from the TCGA and GEO databases. Enrichment analysis indicated that <jats:italic>CKS2<\/jats:italic> functions were primarily linked to protein kinase regulatory activity, G1\/S phase transition of the cell cycle, and the p53 signaling pathway, among others. Second, stable suppression of <jats:italic>CKS2<\/jats:italic> gene expression in Raji and SUDHL6 cells using shRNA resulted in a significant inhibition of cell proliferation. Moreover, <jats:italic>CKS2<\/jats:italic>\u2010shRNA induced G0\/G1 cell cycle arrest and apoptosis by activating the p53 signaling pathway in Raji and SUDHL6 cells. Third, the combined treatment of <jats:italic>CKS2<\/jats:italic>\u2010shRNA and etoposide exhibited a synergistic effect on the proliferation and apoptosis of Raji and SUDHL6 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that <jats:italic>CKS2<\/jats:italic> may play a critical role in the progression of BL and DLBCL and provide evidence for the potential therapeutic application of combining <jats:italic>CKS2<\/jats:italic>\u2010shRNA and etoposide agents in the treatment of BL and DLBCL.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70435","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T12:39:52Z","timestamp":1732019992000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unveiling <scp><i>CKS2<\/i><\/scp>: A Key Player in Aggressive B\u2010Cell Lymphoma Progression and a Target for Synergistic 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