BCL6B expression in hepatocellular carcinoma and its efficacy in the inhibition of liver damage and fibrogenesis
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Weilin Wang1,2,3,*, Pengfei Huang1,3,*, Panyisha Wu2,3, Rong Kong1, Jiang Xu1, Lufei Zhang1, Qifan Yang1, Qingsong Xie1, Linshi Zhang2, Xiaohu Zhou1, Linghui Chen1, Haiyang Xie1,3, Lin Zhou1,3, Shusen Zheng1,2,3
1Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
2Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
3Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
*These authors have contributed equally to this work
Shusen Zheng, e-mail: [email protected]
Keywords: BCL6B, hepatocellular carcinoma, liver fibrosis, prognostic biomarker
Received: February 2, 2015 Accepted: April 14, 2015 Published: April 27, 2015
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.
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