Zhang Pengfei, Dong Zhaoru, Cai Jiabin, Zhang Chi, Shen Zaozhuo, Ke Aiwu, Gao Dongmei, Fan Jia, Shi Guoming
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, PR China Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, PR China.
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, PR China Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, PR China Cancer Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, PR China.
Int J Immunopathol Pharmacol. 2015 Mar;28(1):36-44. doi: 10.1177/0394632015572070.
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.
溴结构域和额外末端结构域（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（HCC）组织中相较于相邻正常组织显著上调。此外，癌组织中BRD4的过表达与HCC患者的不良预后相关。通过在HCC细胞中使用shRNA介导的BRD4敲低或慢病毒介导的BRD4过表达，我们进一步表明BRD4参与了体外HCC细胞的生长和侵袭。BRD4的强制表达足以在HCC细胞中诱导上皮-间质转化（EMT）表型。此外，BRD4 shRNA在体内显著抑制HCC细胞增殖。总体而言，我们的研究证实BRD4表达是HCC患者复发和生存的有价值预测指标。BRD4可进一步用作HCC的潜在治疗靶点。
