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SOX2基因在结直肠癌中的染色质免疫沉淀测序及功能分析

ChIP-seq and Functional Analysis of the SOX2 Gene in Colorectal Cancers.

作者信息

Fang Xuefeng, Yu Wei, Li Lisha, Shao Jiaofang, Zhao Na, Chen Qiyun, Ye Zhiyun, Lin Sheng-Cai, Zheng Shu, Lin Biaoyang

机构信息

1 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, People's Republic of China .

出版信息

OMICS. 2010 Aug 20. doi: 10.1089/omi.2010.0026.

DOI:10.1089/omi.2010.0026
PMID:20726776
Abstract

Abstract SOX2 is a high mobility group (HMG) box containing transcription factor that has been implicated in various types of cancer, but its role in colorectal cancers (CRC) has not been studied. Here we show that SOX2 is overexpressed in CRC tissues compared with normal adjacent tissues using immunohistochemical staining and RT-PCR. We also observed an increased SOX2 expression in nucleus of colorectal cancer tissues (46%, 14/30 cases vs. 7%, 2/30 adjacent tissues). Furthermore, knockdown of SOX2 in SW620 colorectal cancer cells decreased their growth rates in vitro cell line, and in vivo in xenograft models. ChIP-seq analysis of SOX2 revealed a consensus sequence of wwTGywTT. An integrated expression profiling and ChIP-seq analysis show that SOX2 is involved in the BMP signaling pathway, steroid metabolic process, histone modifications, and many receptor-mediated signaling pathways such as IGF1R and ITPR2 (Inositol 1,4,5-triphosphate receptor, type 2).

摘要

摘要

SOX2是一种含有高迁移率族(HMG)盒的转录因子,与多种癌症相关,但它在结直肠癌(CRC)中的作用尚未得到研究。在此,我们通过免疫组织化学染色和逆转录-聚合酶链反应(RT-PCR)表明,与相邻正常组织相比,SOX2在CRC组织中过表达。我们还观察到结直肠癌组织细胞核中SOX2表达增加(46%,14/30例 vs. 7%,2/30例相邻组织)。此外,在SW620结直肠癌细胞中敲低SOX2会降低其在体外细胞系和体内异种移植模型中的生长速率。对SOX2的染色质免疫沉淀测序(ChIP-seq)分析揭示了一个共有序列wwTGywTT。综合表达谱分析和ChIP-seq分析表明,SOX2参与骨形态发生蛋白(BMP)信号通路、类固醇代谢过程、组蛋白修饰以及许多受体介导的信号通路,如胰岛素样生长因子1受体(IGF1R)和肌醇三磷酸受体2(ITPR2)。

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