Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2020
CKS2 modulates cell-cycle progression of tongue squamous cell carcinoma cells partly via modulating the cellular distribution of DUTPase.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Gao Fei, Li Chong, Zhao Xiqun, Xie Jianli, Fang Guiqing, Li Ying
Аннотация
BACKGROUND: CKS2 (CDC28 Protein Kinase Regulatory Subunit 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.
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.