Regulation of XAF1 expression in human colon cancer cell by interferon β:: Activation by the transcription regulator STAT1
Regulation of XAF1 expression in human colon cancer cell by interferon β:: Activation by the transcription regulator STAT1
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DOI：
10.1016/j.canlet.2007.10.014
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发表时间：
2008-02-18
期刊：
影响因子：
9.7
通讯作者：
Wong, Benjamin C. Y.
中科院分区：
文献类型：
--
作者：
Sun, Yunwei;Qiao, Liang;Wong, Benjamin C. Y.
xap相关因子1 （XAF1）是一种新的肿瘤抑制和干扰素刺激基因。干扰素β (IFN β)通过I型干扰素受体（IFN- r）的Jak-Stat信号级联发挥抗增殖作用，诱导细胞凋亡，干扰素β的生物效应因子可启动基因转录。本研究的目的是确定IFN β对XAF1表达的影响，以及由信号转导和转录激活因子1 （Stat1）的关键作用介导的可能机制。采用RT-PCR和Western blot检测基因表达。荧光素酶报告基因法检测XAF1启动子活性。采用电泳迁移位移法（EMSA）和定量染色质免疫沉淀法（Q-ChIP）检测干扰素刺激反应元件（ISRE）的活性。结果表明，IFN β刺激结肠癌细胞系DLD1中XAF1启动子活性呈时间和剂量依赖性。高亲和力ISRE结合元件（ISRE-XAF1）位于XAF1基因第一个ATG位点上游-55 ~ -66 nt。ISRE-XAF1的缺失完全消除了基础启动子和IFN β诱导的启动子活性。Stat1通过与ISRE-XAF1相互作用介导IFN β诱导的XAF1表达。敲低Stat1表达并阻断其磷酸化可降低IFN β诱导的XAF1表达。结果表明，在结肠癌中，转录调节因子Stat1通过XAF1基因启动子区域内的ISRE位点介导IFN β诱导立即早期反应基因XAF1。2007爱思唯尔爱尔兰有限公司版权所有。
XIAP-associated factor 1 (XAF1) is a novel tumor suppressor and interferon stimulated gene (ISG). Interferon beta (IFN beta) exerts anti-proliferative effect and induces apoptosis through the Jak-Stat signaling cascade by the type I Interferon receptor (IFN-R), which initiates gene transcription of those biological effectors of IFN beta. The aim of this study is to determine the effect of IFN beta on XAF1 expression and the putative mechanisms mediated by the critical role of signal transducers and activators of transcription 1 (Stat1). Gene expression was detected by RT-PCR and Western blot analysis. The promoter activity of XAF1 was examined by luciferase reporter assay. The activity of interferon stimulated response element (ISRE) was assessed by electrophoretic mobility shift assay (EMSA) and quantitative chromatin immunoprecipitation assay (Q-ChIP). Results showed that IFN beta stimulated XAF1 promoter activity in colon cancer cell line DLD1 in a time- and dose-dependent manner. A high affinity ISRE binding element (ISRE-XAF1) was located in -55 to -66 nt upstream of the first ATG site of XAF1 gene. Deletion of ISRE-XAF1 completely abrogated basal and IFN beta-induced promoter activity. IFN beta-induced XAF1 expression was mediated by Stat1 through the interaction with ISRE-XAF1. Knocking down of the Stat1 expression and blocking its phosphorylation decreased IFN beta-induced XAF1 expression. Results suggested that induction of an immediate early response gene-XAF1 by IFN beta was mediated by the transcription regulator Stat1 through the ISRE site within the promoter region of XAF1 gene in colon cancer. (C) 2007 Elsevier Ireland Ltd. All rights reserved.