Bromodomain-containing protein 7 (BRD7) as a potential tumor suppressor in hepatocellular carcinoma.
Bromodomain-containing protein 7 (BRD7) as a potential tumor suppressor in hepatocellular carcinoma.
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含溴结构域蛋白 7 (BRD7) 作为肝细胞癌的潜在肿瘤抑制因子
DOI：
10.18632/oncotarget.7637
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发表时间：
2016-03-29
期刊：
影响因子：
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通讯作者：
Xia JC
中科院分区：
文献类型：
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作者：
Chen CL;Wang Y;Pan QZ;Tang Y;Wang QJ;Pan K;Huang LX;He J;Zhao JJ;Jiang SS;Zhang XF;Zhang HX;Zhou ZQ;Weng de S;Xia JC
含溴结构域蛋白7 （BRD7）是PBAF复合物的一个亚基，其功能是肿瘤抑制蛋白p53的转录辅因子。BRD7的下调已在多种类型的癌症中得到证实。本研究旨在探讨BRD7在肝细胞癌（HCC）中的表达及其抑瘤作用。通过实时定量PCR、western blot和免疫组织化学检测BRD7在原发性HCC临床标本和HCC细胞系中的表达。统计学分析BRD7表达的预后价值及其与HCC患者临床病理特征的相关性。BRD7对HCC致瘤性的影响也通过增殖和集落形成实验、细胞周期实验、迁移和细胞侵袭实验以及异种移植裸鼠模型进行了检验。BRD7在肿瘤组织和HCC细胞系中下调。BRD7蛋白表达与临床分期和肿瘤大小密切相关。Kaplan-Meier生存曲线显示，与BRD7表达水平较低的患者相比，BRD7表达水平较高的患者生存率更高。多变量分析表明BRD7表达是一个独立的预后指标。BRD7表达的重新引入显著抑制体外HCC细胞的增殖、集落形成、迁移和侵袭，导致细胞周期阻滞。此外，小鼠实验表明，BRD7过表达在体内抑制HCC的致瘤性。总之，我们的数据表明BRD7可能在HCC中起到抑癌作用，可能是治疗HCC的一个新的分子靶点。
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.