ZBP-89 and Sp1 contribute to Bak expression in hepatocellular carcinoma cells.
ZBP-89 and Sp1 contribute to Bak expression in hepatocellular carcinoma cells.
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ZBP-89 和 Sp1 有助于肝细胞癌细胞中的 Bak 表达。
DOI：
10.1186/s12885-018-4349-y
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发表时间：
2018-04-13
期刊：
影响因子：
3.8
通讯作者：
Ye CG
中科院分区：
文献类型：
--
作者：
Kong X;Xu P;Cai WJ;Wang HG;Li BB;Huang GL;He ZW;Chen G;Ye CG
Kruppel家族成员锌结合蛋白(ZBP-)，也被称为ZNF148，通过与富含GC的启动子区域结合来调节Bak的表达。目前尚不清楚其他富含GC的结合因子，如Sp家族成员，是否能与ZBPp-89在Bak表达上相互作用。本研究旨在通过体外实验和肿瘤基因组图谱(TCGA)肝细胞癌(HCC)数据队列的研究，阐明ZBP-89和Sp蛋白对Bak基因表达的调控机制。我们下载了TCGA肝细胞癌的队列数据，以分析Bak转录水平与ZBP-89和Sp蛋白转录水平的关系。以肝癌细胞系和肝脏永生化非肿瘤细胞系为研究对象，进行免疫印迹分析、表达载体介导的基因表达和siRNA干扰等机制研究。结果表明，癌组织中Bak的转录水平高于癌旁组织。BAK转录水平与Sp1、Sp3的表达水平呈正相关，而ZBP-、Bak、Sp2、Sp4的转录水平与Sp1、Sp3的表达无相关性。米曲霉素A(MMA)以剂量依赖方式诱导Bak表达。Western blotting结果显示，Sp1过表达增加了Bak在肝脏永生化非肿瘤细胞和肝癌细胞中的表达。干扰Sp1的表达可单独抑制Bak的表达。即使在MMA处理和S1过表达的情况下，ZBP-89 siRNA也抑制Bak的表达。此外，Bak和Sp1水平与肝细胞癌患者的生存相关。BAK的表达需要ZBP-和Sp1同时协同调控。本文的在线版本(10.1186/s12885-0184349-y)包含向授权用户提供的补充材料。
Kruppel family member zinc binding protein 89 (ZBP-89), also known as ZNF148, regulates Bak expression via binding to GC-rich promoter domain. It is not clear if other GC-rich binding factors, such as Sp family members, can interact with ZBPp-89 on Bak expression. This study aims to elucidate the mechanism of Bak expression regulation by ZBP-89 and Sp proteins, based on in vitro experiment and The Cancer Genome Atlas (TCGA) hepatocellular carcinoma (HCC) data cohort. We downloaded TCGA hepatocellular carcinoma (HCC) cohort data to analysis the association of Bak transcription level with ZBP-89 and Sp proteins transcription level. HCC cell lines and liver immortal non-tumour cell lines were used for mechanism study, including western blotting analysis, expression vector mediated gene expression and siRNA interference. Results showed that cancer tissues have higher Bak transcription level compared with adjacent non-cancer tissues. Bak transcription level was correlated with Sp1 and Sp3 expression level, while no correlation was found in ZBP-89 and Bak, neither Sp2 nor Sp4. Mithramycin A (MMA) induced Bak expression in a dose-dependent manner. Western blotting results showed Sp1 overexpression increased Bak expression both in liver immortal non-tumour cells and HCC cells. Interference Sp1 expression could inhibit Bak expression alone. ZBP-89 siRNA suppressed Bak expression even in the presence of MMA treatment and S1 overexpression. Additionally, Bak and Sp1 level were associated with HCC patient survival. Bak expression required ZBP-89 and Sp1 cooperative regulation simultaneously. The online version of this article (10.1186/s12885-018-4349-y) contains supplementary material, which is available to authorized users.
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作者：
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