Bromodomain-containing protein 7 (BRD7) as a potential tumor suppressor in hepatocellular carcinoma
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Chang-Long Chen1,2,*, Ying Wang1,3,*, Qiu-Zhong Pan1,2, Yan Tang1,2, Qi-Jing Wang2, Ke Pan1,2, Li-Xi Huang2, Jia He2, Jing-Jing Zhao1,2, Shan-Shan Jiang1,2, Xiao-Fei Zhang1,2, Hong-Xia Zhang1,2, Zi-Qi Zhou1,2, De-Sheng Weng1,2 and Jian-Chuan Xia1,2
1 Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
2 Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, China
3 Department of Epidemiology and Health Statistics, Guangdong Key Laboratory of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China
* These authors have contributed equally to this work
Jian-Chuan Xia, email:
De-Sheng Weng, email:
Keywords: BRD7, tumor suppressor, hepatocellular carcinoma, prognosis, tumorigenicity
Received: December 15, 2015 Accepted: February 08, 2016 Published: February 23, 2016
Bromodomain-containing protein 7 (BRD7) is a subunit of the PBAF complex, which functions as a transcriptional cofactor for the tumor suppressor protein p53. Down-regulation of BRD7 has been demonstrated in multiple types of cancer. This study aimed to investigate BRD7 expression and its tumor suppressive effect in hepatocellular carcinoma (HCC).The expression of BRD7 was examined in clinical specimens of primary HCC and in HCC cell lines through real-time quantitative PCR, western blot and immunohistochemistry. The prognostic value of BRD7 expression and its correlation with the clinicopathological features of HCC patients were statistically analyzed. The effect of BRD7 on the tumorigenicity of HCC was also examined using proliferation and colony-formation assays, cell-cycle assays, migration and cell-invasion assays, and xenograft nude mouse models. BRD7 was down-regulated in tumor tissues and HCC cell lines. BRD7 protein expression was strongly associated with clinical stage and tumor size. Kaplan-Meier survival curves revealed higher survival rates in patients with higher BRD7 expression levels compared to those with lower BRD7 levels. A multivariate analysis indicated that BRD7 expression was an independent prognostic marker. The re-introduction of BRD7 expression significantly inhibited proliferation, colony formation, migration and invasion and led to cell cycle arrest in HCC cells in vitro. Furthermore, experiments in mice suggested that BRD7 overexpression suppresses HCC tumorigenicity in vivo. In conclusions, our data indicated that BRD7 may serve as a tumor suppressor in HCC and may be a novel molecular target for the treatment of HCC.
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