Knockdown of CDCA8 inhibits the proliferation and enhances the apoptosis of bladder cancer cells
Knockdown of CDCA8 inhibits the proliferation and enhances the apoptosis of bladder cancer cells
复制标题
敲除CDCA8可抑制膀胱癌细胞的增殖并增强其凋亡
DOI：
10.7717/peerj.9078
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发表时间：
2020-04-28
期刊：
影响因子：
2.7
通讯作者：
Zhang, Shufang
中科院分区：
文献类型：
--
作者：
Gao, Xin;Wen, Xiaohong;Zhang, Shufang
膀胱癌是一种死亡率很高的泌尿系统肿瘤，临床上也非常缺乏治疗靶点。细胞分裂周期相关蛋白8（CDCA 8）是脊椎动物染色体乘客复合体的重要组成部分，在各种肿瘤中高度表达，并促进肿瘤的发展。然而，CDCA 8在膀胱癌中的作用尚未完全了解。本研究旨在通过检测CDCA 8表达与膀胱癌细胞增殖、转移和凋亡的关系，揭示CDCA 8在膀胱癌中的作用。首先，我们通过GEO和TCGA数据库研究了CDCA 8的mRNA表达，并分析了CDCA 8表达与膀胱癌患者预后的相关性。我们还通过免疫组化证实了CDCA 8在膀胱癌组织中的表达。另外，CDCA 8在膀胱癌T24和5637细胞中的表达受到抑制，并通过细胞计数试剂盒-8、集落形成、细胞周期、凋亡、伤口愈合和Transwell侵袭实验研究了CDCA 8对膀胱癌细胞系增殖、迁移和侵袭的影响。结果显示，CDCA 8在膀胱癌组织中的表达高于正常组织，且CDCA 8的高表达与患者的预后不良显著相关。抑制CDCA 8表达可抑制T24和5637细胞的增殖、迁移和侵袭，并诱导膀胱癌细胞凋亡。CDCA 8参与了膀胱癌细胞生长周期的调控。基于生物信息学的机制分析显示，CDCA 8的高表达可能影响细胞周期和P53信号通路。总之，我们的研究结果表明，CDCA 8在膀胱癌中高表达，并能促进肿瘤的发展。因此，CDCA 8可以作为膀胱癌治疗的有效靶点。
Bladder cancer is a tumour of the urinary system with high mortality, and there is also a great lack of therapeutic targets in the clinic. Cell division cycle associated 8 (CDCA8), an important component of the vertebrate chromosomal passenger complex, is highly expressed in various tumours and promotes tumour development. However, the role of CDCA8 in bladder cancer is not fully understood. This study aimed to reveal the function of CDCA8 in bladder cancer by determining the relationship between CDCA8 expression and proliferation, metastasis and apoptosis of bladder cancer cells. Firstly, we studied the mRNA expression of CDCA8 through the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases and analysed the correlation between CDCA8 expression and prognosis of patients with bladder cancer. We also verified CDCA8 expression in bladder cancer tissues by immunohistochemistry. In addition, CDCA8 expression was inhibited in bladder cancer T24 and 5637 cells, and the effects of CDCA8 on the proliferation, migration and invasion of bladder cancer cell lines were investigated using cell counting kit-8, colony formation, cell cycle, apoptosis, wound healing and Transwell invasion assays. Results showed that CDCA8 was highly expressed in bladder cancer compared with normal tissues, and the high CDCA8 expression was significantly correlated with the poor prognosis of patients. Inhibiting CDCA8 expression inhibited the proliferation, migration and invasion of T24 and 5637 cells and induced the apoptosis of bladder cancer cells. CDCA8 was involved in the regulation of the growth cycle of bladder cancer cells. Bioinformatics-based mechanism analysis revealed that high CDCA8 expression may affect the cell cycle and P53 signalling pathways. In conclusion, our results suggest that CDCA8 is highly expressed in bladder cancer and can promote tumour development. Hence, CDCA8 may serve as an effective therapeutic target for treatment of bladder cancer.