Chen Yincong, Xie Haibiao, Zou Yifan, Lai Xiulan, Ma Lian, Liu Yuchen, Li Jianfa
Shantou University Medical College, Shantou 515041, Guangdong Province, China.
Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China.
Mol Biosyst. 2017 Jul 25;13(8):1597-1607. doi: 10.1039/c7mb00202e.
Previous studies have suggested that EZH2 is up-regulated in bladder cancer tissues and identified it as a biomarker for poor prognosis. However, the biological functions of EZH2 in bladder cancer cells remain unknown. In this research, we discovered that EZH2 expression is irrelevant to the TNM stage and poor prognosis of bladder cancer patients. But suppression of EZH2 can slowdown the progression of bladder cancer cells. Moreover, we used the technology of synthetic biology to construct the tetracycline-controllable artificial microRNA-HOTAIR + EZH2, which can decrease the expression of HOTAIR and EZH2 in a doxycycline dosage-dependent manner. And we also found that HOTAIR expression was positively correlated with EZH2 expression. Tetracycline-controllable artificial microRNA-HOTAIR + EZH2 can inhibit the proliferation and migration of bladder cancer cells. Meanwhile, the apoptosis rate of bladder cancer cells was increased. Taken together, our research showed the cancer-promoting effects of EZH2 and created a novel method to rescue the development of bladder cancer cells.
先前的研究表明,EZH2在膀胱癌组织中上调,并将其确定为预后不良的生物标志物。然而,EZH2在膀胱癌细胞中的生物学功能仍不清楚。在本研究中,我们发现EZH2表达与膀胱癌患者的TNM分期及预后不良无关。但抑制EZH2可减缓膀胱癌细胞的进展。此外,我们利用合成生物学技术构建了四环素可控的人工微小RNA-HOTAIR + EZH2,其可在强力霉素剂量依赖性方式下降低HOTAIR和EZH2的表达。并且我们还发现HOTAIR表达与EZH2表达呈正相关。四环素可控的人工微小RNA-HOTAIR + EZH2可抑制膀胱癌细胞的增殖和迁移。同时,膀胱癌细胞的凋亡率增加。综上所述,我们的研究显示了EZH2的促癌作用,并创造了一种挽救膀胱癌细胞发展的新方法。