Transcriptional regulation and biological functions of selenium-binding protein 1 in colorectal cancer in vitro and in nude mouse xenografts.

Transcriptional regulation and biological functions of selenium-binding protein 1 in colorectal cancer in vitro and in nude mouse xenografts.
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DOI:
10.1371/journal.pone.0007774
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发表时间:
2009-11-16
期刊:
影响因子:
3.7
通讯作者:
Yang W
Yang W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pohl NM;Tong C;Fang W;Bi X;Li T;Yang W

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研究表明,硒结合蛋白1(SBP 1)在不同的人类癌症中显著下调。其管理和职能尚未确立。我们发现,在结肠癌组织和人结肠癌细胞中,SBP 1启动子是高甲基化的。用5′-氮杂-2 ′-脱氧胞苷处理导致人结肠癌细胞中SBP 1启动子的去甲基化和SBP 1启动子活性的增加,挽救了SBP 1 mRNA和蛋白的表达。此外,过表达的SBP 1敏感的结肠癌细胞H2 O2诱导的凋亡,抑制癌细胞在体外迁移和抑制裸鼠肿瘤生长。这些数据表明,SBP 1具有肿瘤抑制功能,在结直肠癌中通过表观遗传沉默被抑制。
It has been shown that selenium-binding protein 1 (SBP1) is significantly downregulated in different human cancers. Its regulation and function have not yet been established. We show that the SBP1 promoter is hypermethylated in colon cancer tissues and human colon cancer cells. Treatment with 5′-Aza-2′-deoxycytidine leads to demethylation of the SBP1 promoter and to an increase of SBP1 promoter activity, rescues SBP1 mRNA and protein expression in human colon cancer cells. Additionally, overexpression of SBP1 sensitizes colon cancer cells to H2O2-induced apoptosis, inhibits cancer cell migration in vitro and inhibits tumor growth in nude mice. These data demonstrate that SBP1 has tumor suppressor functions that are inhibited in colorectal cancer through epigenetic silencing.
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