CKS2 modulates cell-cycle progression of tongue squamous cell carcinoma cells partly via modulating the cellular distribution of DUTPase.

BACKGROUND:CKS2 (CDC28 2) is a gene that encodes CKS2 protein that has been characterized as a binding partner of the catalytic subunit of the cyclin-dependent kinases. However, its expression profile and regulatory effects in tongue squamous cell carcinoma has not yet been explored. METHODS:Bioinformatic analysis was conducted using bulk-seq data from The Cancer Genome Atlas and single-cell RNA-seq data from GSE103322. SCC9 and CAL27 cells were used as in vitro cell models for cellular and molecular studies. RESULTS:CKS2 expression was significantly upregulated in tongue squamous cell carcinoma tissues (N = 128) compared with adjacent normal tissues (N = 13). Its upregulation was associated with significantly shorter disease-specific survival and progression-free survival. Cellular status estimation in tumor cells indicated that CKS2 expression was moderately and positively correlated with cell-cycle progression. CKS2 inhibition in SCC9 and CAL27 cells resulted in decreased proliferation, weakened colony formation capability, and cell-cycle arrest at the G2/M phase. Immunofluorescence staining and co-Immunoprecipitation (co-IP) assay confirmed co-localization and interaction between CKS2 and DUTPase. CKS2 knockdown did not alter DUTPase expression but reduced its nuclear distribution. Both CKS2 and DUT expression were moderately correlated with their gene-level copy number. CONCLUSION:CKS2 expression is associated with unfavorable survival of patients with tongue squamous cell carcinoma. Inhibiting its expression could reduce tongue squamous cell carcinoma cell growth and induce G2/M arrest. CKS2 may interact with DUTPase and regulate its nuclear localization. Gene-level copy amplification might be an important mechanism of upregulated CKS2 and DUT in the tumor.

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