OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma.
OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma.
复制标题
OCT4增加BIRC5和CCND1表达并促进肝细胞癌的癌症进展
DOI：
10.1186/1471-2407-13-82
复制
发表时间：
2013-02-22
期刊：
影响因子：
3.8
通讯作者：
Su C
中科院分区：
文献类型：
--
作者：
Cao L;Li C;Shen S;Yan Y;Ji W;Wang J;Qian H;Jiang X;Li Z;Wu M;Zhang Y;Su C
OCT 4和BIRC 5优先在人癌细胞中表达，并介导癌细胞存活和肿瘤维持。然而，调控OCT4和BIRC 5表达的分子机制尚未得到很好的表征。通过调控肝癌细胞系中OCT4和BIRC 5的表达，研究OCT4对BIRC 5和CCND1的调控机制。增加或减少OCT4的表达可通过调节BIRC 5启动子的活性而分别增强或抑制BIRC 5的表达。由于BIRC 5启动子中没有OCT4的结合位点，因此OCT4对BIRC 5启动子的作用是间接的。CCND1启动子中的OCT4八聚体基序直接和部分参与了CCND1启动子活性的调节，表明OCT4也可以上调CCND1的表达。共抑制OCT4和BIRC 5可诱导癌细胞凋亡和细胞周期阻滞，从而有效抑制癌细胞的增殖活性，并抑制裸鼠中HCC异种移植物的生长。OCT 4可以通过增加其启动子活性来上调BIRC 5和CCND1的表达。这些因素共同促进HCC细胞增殖，并且OCT4和BIRC 5的共抑制对于HCC治疗是潜在有益的。
OCT4 and BIRC5 are preferentially expressed in human cancer cells and mediate cancer cell survival and tumor maintenance. However, the molecular mechanism that regulates OCT4 and BIRC5 expression is not well characterized. By manipulating OCT4 and BIRC5 expression in hepatocellular carcinoma (HCC) cell lines, the regulatory mechanism of OCT4 on BIRC5 and CCND1 were investigated. Increasing or decreasing OCT4 expression could enhance or suppress BIRC5 expression, respectively, by regulating the activity of BIRC5 promoter. Because there is no binding site for OCT4 within BIRC5 promoter, the effect of OCT4 on BIRC5 promoter is indirect. An octamer motif for OCT4 in the CCND1 promoter has directly and partly participated in the regulation of CCND1 promoter activity, suggesting that OCT4 also could upregulated the expression of CCND1. Co-suppression of OCT4 and BIRC5 induced cancer cell apoptosis and cell cycle arrest, thereby efficiently inhibiting the proliferative activity of cancer cells and suppressing the growth of HCC xenogrfts in nude mice. OCT4 can upregulate BIRC5 and CCND1 expression by increasing their promoter activity. These factors collusively promotes HCC cell proliferation, and co-suppression of OCT4 and BIRC5 is potentially beneficial for HCC treatment.
登录
查看更多内容
影响因子：
4.1
作者：
Li, FZ;Altieri, DC
通讯作者：
Altieri, DC
影响因子：
11.2
作者：
Gu, Guangyu;Yuan, Jialing;Kasper, Susan
通讯作者：
Kasper, Susan
影响因子：
11.5
作者：
Chiou, Shih-Hwa;Yu, Cheng-Chia;Lo, Jeng-Fan
通讯作者：
Lo, Jeng-Fan
影响因子：
11.2
作者：
Chang, Chao-Ching;Shieh, Gia-Shing;Wu, Chao-Liang
通讯作者：
Wu, Chao-Liang
影响因子：
11.5
作者：
Mita, Alain C.;Mita, Monica M.;Giles, Francis J.
通讯作者：
Giles, Francis J.