Epigenetic silencing of BCL6B inactivates p53 signaling and causes human hepatocellular carcinoma cell resist to 5-FU.
Epigenetic silencing of BCL6B inactivates p53 signaling and causes human hepatocellular carcinoma cell resist to 5-FU.
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DOI：
10.18632/oncotarget.3413
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Guo M
中科院分区：
文献类型：
--
作者：
Li X;Yu J;Brock MV;Tao Q;Herman JG;Liang P;Guo M
BCL6B在人胃癌中是一种潜在的抑瘤因子，但BCL6B在人肝细胞癌变中的调控及机制尚不清楚。本研究旨在探讨BCL6B在人肝细胞癌（HCC）中的表观遗传变化及其机制。19株肝癌细胞株，50例癌旁组织，149例肝癌标本。BCL6B在100%（19/19）的人HCC细胞系、40.0%（20/50）的邻近组织样本和86.6%（129/149）的原发性癌症样本中甲基化。BCL6B甲基化与HBV阳性相关（p < 0.05）。但与年龄、性别、肿瘤大小、分化程度、TNM分期、复发和生存率无相关性。在19个完全甲基化的HCC细胞系中发现BCL6B表达缺失。5-aza-2 ' -脱氧胞苷处理后BCL6B重新表达。恢复BCL6B表达可抑制细胞增殖，诱导细胞凋亡和G1/S阻滞。在HCC细胞中，BCL6B再表达后，p53信号通路的关键组成部分EGR1的表达增加。BCL6B的重新表达激活了p53信号，使HCC细胞对5-氟尿嘧啶敏感。BCL6B在人类HCC中经常甲基化，BCL6B的表达受启动子区域超甲基化调节。BCL6B通过增加肝癌中EGR1的表达激活p53信号。
BCL6B is a potential tumor suppressor in human gastric cancer, but the regulation and mechanism of BCL6B in human hepatocellular carcinogenesis remain unclear. This study is to explore the epigenetic change and mechanism of BCL6B in human hepatocellular carcinoma (HCC). Nineteen hepatic cancer cell lines, 50 cases of adjacent tissue and 149 cases of HCC samples were employed. BCL6B is methylated in 100% (19/19) of human HCC cell lines, 40.0% (20/50) of adjacent tissue samples and 86.6% (129/149) of primary cancer samples. Methylation of BCL6B is associated with HBV positive (p < 0.05). But no association was found with age, sex, tumor size, differentiation, TNM stage, recurrence and survival. Loss of BCL6B expression was found in 19 of completely methylated HCC cell lines. BCL6B was re-expressed after 5-aza-2′-deoxycytidine treatment. Restoration of BCL6B expression suppressed cell proliferation, induced apoptosis and G1/S arrest in HCC cells. The expression of EGR1, a key component of p53 signaling, was increased after re-expression BCL6B in HCC cells. Re-expression of BCL6B activated p53 signaling and sensitized HCC cells to 5-fluorouracil. BCL6B is frequently methylated in human HCC and the expression of BCL6B is regulated by promoter region hypermethylation. BCL6B activates p53 signaling by increasing EGR1 expression in HCC.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
7.3
作者：
Jia, Yan;Yang, Yunsheng;Brock, Malcolm V.;Zhan, Qimin;Herman, James G.;Guo, Mingzhou
通讯作者：
Guo, Mingzhou
影响因子：
5.7
作者：
Deng, Ying-Bing;Nagae, Genta;Kaneda, Atsushi
通讯作者：
Kaneda, Atsushi
影响因子：
82.9
作者：
Pan, Xin;Zhou, Tao;Zhang, Xue-Min
通讯作者：
Zhang, Xue-Min
影响因子：
8
作者：
Lee, JO;Kwun, HJ;Jang, KL
通讯作者：
Jang, KL