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

Wu H, Zhu S, Mo YY - Cell Res. (2009)

Bottom Line: In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 825 N. Rutledge, PO Box 19626, Springfield, IL 62794, USA.

ABSTRACT
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.

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miR-205 inhibits cell invasion and metastasisMDA-MB-231 cells were first infected with miR-205 or vector alone and then were tested for invasion ability in matrigel chambers or metastasis in nude mice as described in Materials and Methods. A and B, In vitro cell invasion assays with representative fields of invaded cells. Values in A are means of three experiments ± SE. **, p < 0.01. C, Effect of miR-205 on tumor metastasis. *, p <0.05. D, Representative lungs harvested from the nude mice. Arrows indicate some of tumor nodules.
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Figure 4: miR-205 inhibits cell invasion and metastasisMDA-MB-231 cells were first infected with miR-205 or vector alone and then were tested for invasion ability in matrigel chambers or metastasis in nude mice as described in Materials and Methods. A and B, In vitro cell invasion assays with representative fields of invaded cells. Values in A are means of three experiments ± SE. **, p < 0.01. C, Effect of miR-205 on tumor metastasis. *, p <0.05. D, Representative lungs harvested from the nude mice. Arrows indicate some of tumor nodules.

Mentions: Based on miRNA profiling data, breast cancers without vascular invasion show high miR-205 expression compared to breast cancers with vascular invasion (21). Furthermore, a recent report indicates that miR-205 is dramatically downregulated in cells undergoing epithelial to mesenchymal transition (EMT) (32). These results suggest that miR-205 may also play a role in cell invasion. To test this hypothesis, we chose a metastatic breast cancer cell line MDA-MB-231 because MDA-MB-231 cells also expressed a low level of miR-205. Matrigel chamber assays indicated that the invasion ability of MDA-MB-231 cells was substantially reduced by miR-205 (Fig. 4 A and B). Since invasion is one of the key steps in metastasis (33), suppression of invasion by miR-205 in MDA-MB-231 cells suggests that miR-205 may also affect breast cancer metastasis. In vivo metastasis assays supported this notion (Fig. 4 C and D). For example, while average number of lung nodules in the miR-205 cells was about 24, this number was only about 2 in the vector control cells.


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

Wu H, Zhu S, Mo YY - Cell Res. (2009)

miR-205 inhibits cell invasion and metastasisMDA-MB-231 cells were first infected with miR-205 or vector alone and then were tested for invasion ability in matrigel chambers or metastasis in nude mice as described in Materials and Methods. A and B, In vitro cell invasion assays with representative fields of invaded cells. Values in A are means of three experiments ± SE. **, p < 0.01. C, Effect of miR-205 on tumor metastasis. *, p <0.05. D, Representative lungs harvested from the nude mice. Arrows indicate some of tumor nodules.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2664859&req=5

Figure 4: miR-205 inhibits cell invasion and metastasisMDA-MB-231 cells were first infected with miR-205 or vector alone and then were tested for invasion ability in matrigel chambers or metastasis in nude mice as described in Materials and Methods. A and B, In vitro cell invasion assays with representative fields of invaded cells. Values in A are means of three experiments ± SE. **, p < 0.01. C, Effect of miR-205 on tumor metastasis. *, p <0.05. D, Representative lungs harvested from the nude mice. Arrows indicate some of tumor nodules.
Mentions: Based on miRNA profiling data, breast cancers without vascular invasion show high miR-205 expression compared to breast cancers with vascular invasion (21). Furthermore, a recent report indicates that miR-205 is dramatically downregulated in cells undergoing epithelial to mesenchymal transition (EMT) (32). These results suggest that miR-205 may also play a role in cell invasion. To test this hypothesis, we chose a metastatic breast cancer cell line MDA-MB-231 because MDA-MB-231 cells also expressed a low level of miR-205. Matrigel chamber assays indicated that the invasion ability of MDA-MB-231 cells was substantially reduced by miR-205 (Fig. 4 A and B). Since invasion is one of the key steps in metastasis (33), suppression of invasion by miR-205 in MDA-MB-231 cells suggests that miR-205 may also affect breast cancer metastasis. In vivo metastasis assays supported this notion (Fig. 4 C and D). For example, while average number of lung nodules in the miR-205 cells was about 24, this number was only about 2 in the vector control cells.

Bottom Line: In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 825 N. Rutledge, PO Box 19626, Springfield, IL 62794, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus