Suppression of cell growth and invasion by miR-205 in breast cancer.
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.
Wu
Hailong
H
Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 825 N. Rutledge, PO Box 19626, Springfield, IL 62794, USA.
Zhu
Shoumin
S
Mo
Yin-Yuan
YY
D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D023421:Models, Animal; D009361:Neoplasm Invasiveness; D020893:Receptor, ErbB-3 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020413:3' Untranslated Regions; D035683:MicroRNAs; D020893:Receptor, ErbB-3; D042461:Vascular Endothelial Growth Factor A; C534425:MIR205, human