期刊
ONCOGENE
卷 33, 期 34, 页码 4307-4315出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2013.381
关键词
DAB2; miRNA; miR-93; lung cancer
资金
- Lung Cancer SPORE from NCI [P50 CA70907]
- Department of Defense [W81XWH-07-1-0306]
- Sun Microsystems [EDUD-7824-021007-US]
- Cancer Center [P30 CA054174, P30 CA142543, P30 CA016672]
- [R01 CA129632]
The disabled homolog 2 (DAB2) gene was recently identified as a tumor suppressor gene with its expression downregulated in multiple cancer types. The role of DAB2 in lung tumorigenesis, however, is not fully characterized, and the mechanisms of DAB2 dysregulation in lung cancer are not defined. Here we show that low DAB2 levels in lung tumor specimens are significantly correlated with poor patient survival, and that DAB2 overexpression significantly inhibits cell growth in cultured lung cancer cells, indicating its potent tumor suppressor function. We next identify that microRNA miR-93 functions as a potent repressor of DAB2 expression by directly targeting the 3'UTR of the DAB2 mRNA. Using in vitro and in vivo approaches, we demonstrate that miR-93 overexpression has an important role in promoting lung cancer cell growth, and that its oncogenic function is primarily mediated by downregulating DAB2 expression. Our clinical investigations further indicate that high tumor levels of miR-93 are correlated with poor survival of lung cancer patients. The correlations of both low DAB2 and high miR-93 expression levels with poor patient survival strongly support the critical role of the miR-93/DAB2 pathway in determining lung cancer progression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据