BRD4 promotes tumor growth and epithelial-mesenchymal transition in hepatocellular carcinoma
BRD4 promotes tumor growth and epithelial-mesenchymal transition in hepatocellular carcinoma
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BRD4促进肝细胞癌中的肿瘤生长和上皮间质转化
DOI：
10.1177/0394632015572070
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发表时间：
2015-03-01
影响因子：
3.5
通讯作者：
Shi, Guoming
中科院分区：
文献类型：
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作者：
Zhang, Pengfei;Dong, Zhaoru;Shi, Guoming
溴结构域和端外结构域(BET)蛋白是表观遗传阅读器，在染色质重塑和转录调控中发挥重要作用。在本研究中，我们发现BET家族成员BRD4在肝细胞癌组织中的表达显著高于癌旁正常组织。此外，BRD4在癌组织中的过度表达与肝细胞癌患者的预后不良有关。通过shRNA介导的BRD4下调或慢病毒介导的BRD4在肝癌细胞中的过表达，我们进一步证明BRD4参与了肝癌细胞的体外生长和侵袭。BRD4的强制表达足以诱导肝癌细胞的上皮-间充质转化(EMT)表型。此外，BRD4 shRNA在体内可显著抑制肝癌细胞的增殖。总体而言，我们的研究证实BRD4的表达是预测肝细胞癌患者复发和生存的有价值的指标。BRD4可进一步作为肝癌的潜在治疗靶点。
Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that play an important role in chromatin remodeling and transcriptional regulation. In this study, we found that BRD4, a BET family member, is significantly upregulated in hepatocellular carcinoma (HCC) tissues compared with adjacent normal tissues. Furthermore, the overexpression of BRD4 in cancer tissues was correlated with poor prognosis in HCC patients. Using shRNA-mediated knockdown of BRD4 or lentivirus-mediated overexpression of BRD4 in HCC cells, we further showed that BRD4 was involved in HCC cell growth and invasion in vitro. Forced expression of BRD4 was sufficient to induce epithelial-mesenchymal transition (EMT) phenotypes in HCC cells. Additionally, BRD4 shRNA significantly inhibited HCC cell proliferation in vivo. Collectively, our study confirmed that BRD4 expression is a valuable predictor of recurrence and survival in patients with HCC. BRD4 can be further used as a potential therapeutic target of HCC.