Chk1-induced CCNB1 overexpression promotes cell proliferation and tumor growth in human colorectal cancer
Chk1-induced CCNB1 overexpression promotes cell proliferation and tumor growth in human colorectal cancer
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DOI：
10.4161/cbt.29691
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发表时间：
2014-01-01
影响因子：
3.6
通讯作者：
Cai, Xiujun
中科院分区：
文献类型：
--
作者：
Fang, Yifeng;Yu, Hong;Cai, Xiujun
结直肠癌的高发病率和高死亡率是世界范围内一个重大的公共卫生问题。本研究评估了CCNB1在不同结直肠癌细胞中的促癌作用及其机制。我们提供的证据表明，CCNB1 mRNA和蛋白水平在人类结直肠肿瘤的一个亚群中上调，并与Chk1表达呈正相关。Chk1的抑制导致结直肠癌细胞增殖和CCNB1蛋白表达显著降低。此外，CCNB1的下调抑制了结直肠癌的体外增殖和体内肿瘤的生长。具体来说，抑制CCNB1在HCT116和SW480细胞中引起强烈的G(2)/M期阻滞，干扰cdc25c和CDK1的表达。此外，CCNB1抑制可诱导某些结直肠癌细胞凋亡。综上所述，这些结果表明CCNB1被Chk1激活，在结直肠癌细胞中发挥其致癌作用，并可能在开发一种新的结直肠癌治疗方法中发挥关键作用。
The high morbidity and mortality of colorectal cancer pose a significant public health problem worldwide. Here we assessed the pro-cancer efficacy and mechanism of action of CCNB1 in different colorectal cancer cells. We provided evidence that CCNB1 mRNA and protein level were upregulated in a subset of human colorectal tumors, and positively correlated with Chk1 expression. Repression of Chk1 caused a significant decrease in cell proliferation and CCNB1 protein expression in colorectal cancer cells. Furthermore, downregulation of CCNB1 impaired colorectal cancer proliferation in vitro and tumor growth in vivo. Specifically, suppression of CCNB1 caused a strong G(2)/M phase arrest in both HCT116 and SW480 cells, interfering with the expression of cdc25c and CDK1. Additionally, CCNB1 inhibition induced apoptotic death in certain colorectal cancer cells. Together, these results suggest that CCNB1 is activated by Chk1, exerts its oncogenic role in colorectal cancer cells, and may play a key role in the development of a novel therapeutic approach against colorectal cancer.