He Jingyang, Huang Yuan, Liu Zhongjian, Zhao Rongce, Liu Qiuying, Wei Ling, Yu Xiaoqin, Li Bo, Qin Yang
Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
Division of Liver Transplantation, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.
Gene. 2017 Sep 20;629:29-34. doi: 10.1016/j.gene.2017.07.077. Epub 2017 Jul 29.
The brother of the regulator of the imprinted site (BORIS), an 11 zinc finger (ZF) protein, is a paralogue of CCCTC-binding factor (CTCF), involves in a few crucial events of chromatin functions, complex transcription regulation during spermatogenesis. As a novel tumor oncogene, abnormal expression of BORIS is observed in human hepatocellular carcinoma, however, the underlying mechanisms remain largely unexplored. In this study, the methylation status of BORIS was tested by methylation specific polymerase chain reaction (MSP) in human HCC cell lines and 43 pairs of tissue specimens. Frequently demethylation of BORIS in HCC was significantly higher than that in the paired adjacent non-tumor tissues (P=0.019), and it was correlated with tumor size (P=0.025) and clinical TNM stage (P=0.035). Patients with hypomethylated BORIS had a shorter disease free survival than those without demethylated BORIS (P=0.006). Further, analyses using Cox regression have indicated that the BORIS demethylation status was an independent risk to the reduced overall survival rate of HCC patients (P=0.035). These findings provide clues to clarify whether the demethylation may lead to activation of the promoter for upregulation expression of BORIS. In conclusions, aberrant BORIS hypomethylation is a promising biomarker for the prognosis of HCC.
印记位点调控因子的兄弟蛋白(BORIS)是一种含有11个锌指(ZF)的蛋白质,是CCCTC结合因子(CTCF)的旁系同源物,参与染色质功能的一些关键事件以及精子发生过程中的复杂转录调控。作为一种新型肿瘤癌基因,在人类肝细胞癌中观察到BORIS的异常表达,然而,其潜在机制在很大程度上仍未被探索。在本研究中,通过甲基化特异性聚合酶链反应(MSP)检测了人类肝癌细胞系和43对组织标本中BORIS的甲基化状态。肝癌中BORIS的频繁去甲基化显著高于配对的相邻非肿瘤组织(P = 0.019),并且与肿瘤大小(P = 0.025)和临床TNM分期(P = 0.035)相关。BORIS低甲基化的患者无病生存期比未发生去甲基化的患者短(P = 0.006)。此外,使用Cox回归分析表明,BORIS去甲基化状态是肝癌患者总生存率降低的独立危险因素(P = 0.035)。这些发现为阐明去甲基化是否可能导致BORIS启动子激活并上调其表达提供了线索。总之,异常的BORIS低甲基化是肝癌预后的一个有前景的生物标志物。