Y-box binding protein-1 (YB-1) promotes cell cycle progression through CDC6-dependent pathway in human cancer cells
Y-box binding protein-1 (YB-1) promotes cell cycle progression through CDC6-dependent pathway in human cancer cells
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DOI：
10.1016/j.ejca.2009.12.024
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发表时间：
2010-03-01
影响因子：
8.4
通讯作者：
Kuwano, Michihiko
中科院分区：
文献类型：
--
作者：
Basaki, Yuji;Taguchi, Ken-ichi;Kuwano, Michihiko
Y-box结合蛋白-1（YB-1）通过转录激活耐药基因和生长因子受体基因在获得整体耐药性和促进细胞生长中起关键作用。在这项研究中，我们研究了YB-1是否参与调节人类癌细胞的细胞周期和细胞增殖。用YB-1 siRNA处理引起癌细胞的细胞增殖和细胞周期相关基因CDC 6的表达的显著抑制。在癌细胞的细胞周期中，通过敲低YB-1特异性地减少S期含量。CDC 6的过表达消除了这种对细胞增殖和S期进入的抑制。ChIP检测表明YB-1与CDC 6基因启动子区的Y-box结合。当用YB-1 siRNA处理时，细胞周期蛋白D1、CDK 1和CDK 2的表达也降低，而p21（Cip 1）和p16（INK 4A）的表达增加。此外，在乳腺癌患者中，细胞核YB-1的表达与细胞核CDC 6的表达水平显著相关。总之，YB-1在人癌细胞G1/S期细胞周期进程中起重要作用。因此，YB-1可能是肿瘤生长和细胞周期的有效生物标志物，与CDC 6密切相关。(C)2009爱思唯尔有限公司保留所有权利。
Y-box binding protein-1 (YB-1) plays pivotal roles in acquisition of global drug resistance and cell growth promotion through transcriptional activation of genes for both drug resistance and growth factor receptors. In this study, we investigated whether YB-1 is involved in regulation of the cell cycle and cell proliferation of human cancer cells. Treatment with YB-1 siRNA caused a marked suppression of cell proliferation and expression of a cell cycle related gene, CDC6 by cancer cells. Of cell cycle of cancer cells, S phase content was specifically reduced by knockdown of YB-1. The overexpression of CDC6 abrogated this inhibition of both cell proliferation and S phase entry. ChIP assay demonstrated that YB-1 binds to a Y-box located in the promoter region of the CDC6 gene. Expression of cyclin D1, CDK1 and CDK2 was also reduced with increased expression of p21(Cip1) and p16(INK4A) when treated with YB-1 siRNA. Furthermore, the nuclear YB-1 expression was significantly associated with the level of CDC6 nuclear expression in patients with breast cancer. In conclusion, YB-1 plays an important role in cell cycle progression at G1/S of human cancer cells. YB-1 thus could be a potent biomarker for tumour growth and cell cycle in its close association with CDC6. (C) 2009 Elsevier Ltd. All rights reserved.