Wang Weilin, Huang Pengfei, Wu Panyisha, Kong Rong, Xu Jiang, Zhang Lufei, Yang Qifan, Xie Qingsong, Zhang Linshi, Zhou Xiaohu, Chen Linghui, Xie Haiyang, Zhou Lin, Zheng Shusen
Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Oncotarget. 2015 Aug 21;6(24):20252-65. doi: 10.18632/oncotarget.3857.
B cell CLL/lymphoma 6 member B (BCL6B) is expressed in many normal tissues but expressed at very low levels in cancer tissues. It was reported that BCL6B inhibits hepatocellular carcinoma (HCC) metastases, but the exact role of BCL6B in HCC remains to be investigated. BCL6B expression was significantly decreased in HCC tissues compared with paired non-cancer tissues. Low BCL6B expression in tumors was correlated with shorter overall survival in patients, and multivariate Cox regression analysis revealed that BCL6B expression was an independent prognostic factor for human HCC patients. Moreover, a positive correlation between BCL6B expression and hepatic cirrhosis was found in an analysis of HCC clinicopathological characteristics. BCL6B expression was increased in rat fibrotic liver samples in response to liver injury. BCL6B transgenic rats were less susceptible to hepatocellular damage, inflammation and fibrosis. In vitro studies demonstrated that BCL6B inhibited the activation of hepatic stellate cells though upregulation of hepatocyte growth factor. In addition, transcriptomic microarray analysis was performed to explore the mechanisms in which BCL6B confers protection from tumorigenesis. In conclusion, BCL6B plays a pivotal role as a prognostic biomarker for HCC, and the restoration of BCL6B may be a novel strategy as an anti-fibrogenic therapy for human HCC.
B细胞慢性淋巴细胞白血病/淋巴瘤6成员B（BCL6B）在许多正常组织中表达，但在癌组织中表达水平极低。据报道，BCL6B抑制肝细胞癌（HCC）转移，但其在HCC中的确切作用仍有待研究。与配对的非癌组织相比，HCC组织中BCL6B表达显著降低。肿瘤中BCL6B低表达与患者较短的总生存期相关，多因素Cox回归分析显示BCL6B表达是人类HCC患者的独立预后因素。此外，在对HCC临床病理特征的分析中发现BCL6B表达与肝硬化呈正相关。在大鼠肝纤维化样本中，BCL6B表达随肝损伤而增加。BCL6B转基因大鼠对肝细胞损伤、炎症和纤维化的易感性较低。体外研究表明，BCL6B通过上调肝细胞生长因子抑制肝星状细胞的激活。此外，进行了转录组微阵列分析以探索BCL6B赋予肿瘤发生保护作用的机制。总之，BCL6B作为HCC的预后生物标志物起着关键作用，恢复BCL6B可能是一种针对人类HCC的新型抗纤维化治疗策略。
