Yuan Gang-Jun, Chen Xin, Lu Jun, Feng Zi-Hao, Chen Si-Liang, Chen Ri-Xin, Wei Wen-Su, Zhou Fang-Jian, Xie Dan
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Cancer Sci. 2017 Nov;108(11):2166-2175. doi: 10.1111/cas.13383. Epub 2017 Sep 25.
Chromobox homolog 8 (CBX8), also known as human polycomb 8, is a repressor that maintains the transcriptionally repressive state in various cellular genes, and has been reported to promote tumorigenesis. In the present study, we examined CBX8 expression in eight pairs of muscle invasive bladder cancer tissues and adjacent non-tumor tissues, and found that CBX8 was frequently upregulated in muscle invasive bladder cancer tissues when compared to adjacent non-tumor tissues. Analysis showed that high expression of CBX8 in 152 muscle invasive bladder cancer specimens was associated with progression of the T, N, and M stages (P = 0.004, 0.005, <0.001, respectively). Furthermore, Kaplan-Meier survival analysis and log-rank test showed that muscle invasive bladder cancer patients with high CBX8 expression had a poor rate of overall survival (P < 0.001) and 5-year recurrence-free survival (P < 0.001) compared to patients with low CBX8 expression. High CBX8 expression predicted poor overall survival and 5-year recurrence-free survival in T and N stages of muscle invasive bladder cancer patients. Moreover, knockdown of CBX8 inhibited cell proliferation of urothelial carcinoma of the bladder both in vitro and in vivo. In addition, CBX8 depletion resulted in cell cycle delay of urothelial carcinoma cells of the bladder at the G2/M phase by the p53 pathway. The data suggest that high expression of CBX8 plays a critical oncogenic role in aggressiveness of urothelial carcinoma cells of the bladder through promoting cancer cell proliferation by repressing the p53 pathway, and CBX8 could be used as a novel predictor for muscle invasive bladder cancer patients.
染色体盒同源物8（CBX8），也称为人类多梳蛋白8，是一种阻遏物，可维持多种细胞基因的转录抑制状态，并且据报道可促进肿瘤发生。在本研究中，我们检测了8对肌肉浸润性膀胱癌组织和相邻非肿瘤组织中CBX8的表达，发现与相邻非肿瘤组织相比，CBX8在肌肉浸润性膀胱癌组织中经常上调。分析表明，152例肌肉浸润性膀胱癌标本中CBX8的高表达与T、N和M分期的进展相关（P分别为0.004、0.005、<0.001）。此外，Kaplan-Meier生存分析和对数秩检验表明，与CBX8低表达的患者相比，CBX8高表达的肌肉浸润性膀胱癌患者的总生存率（P<0.001）和5年无复发生存率（P<0.001）较差。CBX8高表达预示着肌肉浸润性膀胱癌患者在T和N分期的总生存率和5年无复发生存率较差。此外，敲低CBX8在体外和体内均抑制膀胱尿路上皮癌的细胞增殖。此外，CBX8的缺失通过p53途径导致膀胱尿路上皮癌细胞在G2/M期的细胞周期延迟。数据表明，CBX8的高表达通过抑制p53途径促进癌细胞增殖，在膀胱尿路上皮癌细胞的侵袭性中起关键的致癌作用，并且CBX8可作为肌肉浸润性膀胱癌患者的一种新型预测指标。
