ORIGINAL ARTICLE

Cell Research (2009): 439-448
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Suppression of cell growth and invasion by miR-205 in breast cancer

Hailong Wu, Shoumin Zhu and Yin-Yuan Mo

Correspondence: Yin-Yuan Mo, Tel: +1-217-545-8508 E-mail: ymo@siumed.edu

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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-MB-231, 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.

Cell Research (2009) 19:439–448. doi: 10.1038/cr.2009.18; published online 24 February 2009

Keywords: breast cancer, cell growth, ErbB3, miRNA, miR-205, post-transcriptional regulation, VEGF-A