Suppression of cell growth and invasion by miR-205 in breast cancer

被引:283
|
作者
Wu, Hailong [1 ]
Zhu, Shoumin [1 ]
Mo, Yin-Yuan [1 ]
机构
[1] So Illinois Univ, Sch Med, Dept Med Microbiol Immunol & Cell Biol, Springfield, IL 62794 USA
关键词
breast cancer; cell growth; ErbB3; miRNA; miR-205; post-transcriptional regulation; VEGF-A; ANCHORAGE-INDEPENDENT GROWTH; HUMAN MICRORNA GENES; DOWN-REGULATION; EXPRESSION; TARGETS; ERBB3; SEED; METASTASIS; RNAS; TRANSCRIPTS;
D O I
10.1038/cr.2009.18
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR-205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A (VEGF-A) are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3'-untranslated region (3'-UTR) of ErbB3 and VEGF-A. Together, these results suggest that miR-205 is a tumor suppressor in breast cancer.
引用
收藏
页码:439 / 448
页数:10
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