EZH2 elevates the proliferation of human cholangiocarcinoma cells through the downregulation of RUNX3
EZH2 elevates the proliferation of human cholangiocarcinoma cells through the downregulation of RUNX3
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EZH2 通过下调 RUNX3 提高人胆管癌细胞的增殖
DOI：
10.1007/s12032-014-0271-6
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发表时间：
2014-11-01
期刊：
影响因子：
3.4
通讯作者：
He, Songqing
中科院分区：
文献类型：
--
作者：
Tang, Bo;Du, Jian;He, Songqing
探讨组蛋白甲基转移酶增强子zeste同源物2（EZH 2）对人胆管癌细胞增殖和凋亡的影响及其相关机制。应用免疫组化和Western blot方法检测40例胆管癌组织和4株胆管癌细胞中EZH2的表达。通过敲低实验评估EZH2对细胞生长和凋亡的影响，并在裸鼠中进行异种移植实验以评估siEZH2对肿瘤细胞致瘤性的影响。分析EZH2与临床病理特征及总生存率的相关性。EZH2在人胆管癌组织和细胞中高表达。沉默EZH2基因可显著降低人胆管癌细胞RUNX3 DNA甲基化水平，提高其蛋白表达，抑制细胞增殖，诱导细胞凋亡，减缓裸鼠肿瘤生长。EZH2的表达与肿瘤的分期、淋巴结转移及淋巴结转移有关。EZH2的过表达可促进胆管癌细胞的增殖并抑制其凋亡。它与胆管癌患者的预后不良有关。因此，EZH2可能成为胆管癌治疗的潜在临床靶点。
To investigate the impact of histone methyltransferase enhancer of zeste homolog 2 (EZH2) on the proliferation and apoptosis of human cholangiocarcinoma cells as well as its related mechanisms. Immunohistochemistry and Western blot analyses were used to examine the expression of EZH2 in 40 cases of human cholangiocarcinoma tissues and four strains of human cholangiocarcinoma cells. The influence of EZH2 on cell growth and apoptosis were assessed by knockdown experiments, and a xenograft experiment in nude mice was performed to evaluate the impact of siEZH2 on the tumorigenicity of tumor cells. The correlation of EZH2, clinic pathological features and overall survival rates was also analyzed. EZH2 was highly expressed in human cholangiocarcinoma tissues and cells. Silencing of EZH2 could significantly reduce the methylation level of RUNX3 DNA in human cholangiocarcinoma cells and improve its protein expression as well as inhibit cell proliferation, induce apoptosis and slow down the growth of tumor in nude mice. In addition, the expression of EZH2 was associated with the tumor stage, lymph node positivity and poor prognoses. Overexpression of EZH2 can promote the proliferation of cholangiocarcinoma cells and inhibit their apoptosis. It is associated with poor prognoses in patients with cholangiocarcinoma. Therefore, EZH2 could be a potential clinical therapeutic target for the treatment of cholangiocarcinoma.