Downregulation of BRD4 inhibits gallbladder cancer proliferation and metastasis and induces apoptosis via PI3K/AKT pathway.
Downregulation of BRD4 inhibits gallbladder cancer proliferation and metastasis and induces apoptosis via PI3K/AKT pathway.
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BRD4下调抑制胆囊癌增殖和转移并通过PI3K/AKT途径诱导细胞凋亡
DOI：
10.3892/ijo.2017.4081
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发表时间：
2017-09
影响因子：
5.2
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Hao J;Yang Z;Wang L;Zhang Y;Shu Y;Jiang L;Hu Y;Lv W;Dong P;Liu Y
溴域包含蛋白4(BRD4)已被证明在肿瘤进展中起关键作用。然而，BRD4在胆囊癌(GBC)中的表达和功能仍不清楚。在本研究中，我们报道BRD4在GBC组织和GBC细胞系中的表达水平显著上调。探讨BRD4水平与胆囊癌患者临床病理资料的相关性。BRD4的高表达与GBC患者的不良预后显著相关。BRD4基因敲除可抑制NOZ和EH-GB1细胞的增殖和迁移。BRD4基因缺失导致GBC细胞明显凋亡，并下调Bcl2、p-PI3K和p-AKT的表达水平。在体内，BRD4沉默组裸鼠的肿瘤体积明显减小。我们的结果提示BRD4在GBC细胞中的下调通过PI3K/AKT通路诱导细胞凋亡。抑制BRD4的表达可能是治疗GBC的一种新策略。
Bromodomain containing protein 4 (BRD4) has been demonstrated to play a critical role in tumor progression. However, the expression and function of BRD4 in gallbladder cancer (GBC) are still unknown. In this study, we report that BRD4 expression level was significantly upregulated in GBC tissues and GBC cell lines. We explored the correlation between BRD4 levels and clinicopathological data of GBC patients. The high expression level of BRD4 was notably correlated with the poor prognosis of GBC patients. Knockdown of BRD4 suppressed proliferation and migration in NOZ and EH-GB1 cells. The depletion of BRD4 in GBC cell lines resulted in obvious cell apoptosis and downregulated the expression levels of Bcl-2, p-PI3K and p-AKT. In vivo, tumor volumes of nude mice were significantly decreased in BRD4 silenced group. Our data suggested that downregulation of BRD4 in GBC cells induced apoptosis by PI3K/AKT pathway. Inhibition of BRD4 expression may be a novel therapeutic strategy for patients with GBC.
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影响因子：
5.6
作者：
Hu Y;Zhou J;Ye F;Xiong H;Peng L;Zheng Z;Xu F;Cui M;Wei C;Wang X;Wang Z;Zhu H;Lee P;Zhou M;Jiang B;Zhang DY
通讯作者：
Zhang DY
影响因子：
64.5
作者：
Yang, J;Mani, SA;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
5.2
作者：
Meseure, Didier;Vacher, Sophie;Bieche, Ivan
通讯作者：
Bieche, Ivan
影响因子：
5.7
作者：
Togel, Lars;Nightingale, Rebecca;Mariadason, John M.
通讯作者：
Mariadason, John M.
影响因子：
--
作者：
Lu W;Hu Y;Ma Q;Zhou L;Jiang L;Li Z;Zhao S;Xu Y;Shi W;Li S;Liu Y
通讯作者：
Liu Y