Knockdown of CDCA8 inhibits the proliferation and enhances the apoptosis of bladder cancer cells.

Changshun Yang,Mei Chen,Xiaohong Wen,Haowei He,Yibo Yang,Yinyi Chen,Linlin Zheng,Xiguo Zhou,Jinlian Yang,Haifang Liu,Xin Gao,Shufang Zhang

doi:10.7717/peerj.9078

Abstract

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.

Highlights

Bladder cancer is a common malignant tumour in the urinary system and has high mortality and recurrence rates
The clone formation ability of T24 and 5637 cell lines was significantly inhibited in si-Cell division cycle associated 8 (CDCA8) group compared with si-NC group (Figs. 5C–5G; P < 0.001). These results suggest that CDCA8 expression knockdown can inhibit the proliferation of bladder cancer cells
We studied the effect of CDCA8 expression knockdown on cell cycle in T24 and 5637 cell lines, we found that knocking down CDCA8 expression can lead to S and G2/M phase arrest and inhibit the proliferation of bladder cancer cells

Summary

Introduction

Bladder cancer is a common malignant tumour in the urinary system and has high mortality and recurrence rates. The transurethral resection of bladder tumour is a common surgical method for noninvasive bladder cancer; the recurrence rate is high after the operation. The recurrence rate of patients with high-grade bladder cancer can reach 50% within 1 year after operation (Lightfoot et al, 2014). Urine cytology is one of the first choices for diagnosis of bladder cancer This method is less sensitive to the diagnosis of low-grade bladder cancer (Yafi et al, 2015). These conditions highlight the urgent need for new biomarkers to accurately predict the recurrence of bladder cancer. Biomarkers related to the occurrence, development and prognosis of bladder cancer must be identified

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Conclusion