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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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Related in: MedlinePlus

Expression of miR-205 in breast cancer specimens and breast cancer cell linesmiR-205 expression was determined by TaqMan real-time PCR method as described in Materials and Method. Relative CT value (A) or relative expression level of miR-205 (B) in the matched breast tumors and normal breast tissue. C, Relative expression of miR-205 in breast cancer cell lines compared to non-malignant MCF-10A cells from three separate experiments (mean ± SE). **, p < 0.01.
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Figure 1: Expression of miR-205 in breast cancer specimens and breast cancer cell linesmiR-205 expression was determined by TaqMan real-time PCR method as described in Materials and Method. Relative CT value (A) or relative expression level of miR-205 (B) in the matched breast tumors and normal breast tissue. C, Relative expression of miR-205 in breast cancer cell lines compared to non-malignant MCF-10A cells from three separate experiments (mean ± SE). **, p < 0.01.

Mentions: Accumulating evidence indicates that miRNAs can function as oncogenes or tumor suppressors by targeting corresponding tumor suppressor genes or oncogenes (28). To determine the role of miRNAs in breast cancer, we profiled miRNA expression in matched breast tumor specimens by using miRNA TaqMan real-time PCR. We previously showed that the oncogenic miR-21 was more highly expressed in the breast tumors than in the matched normal breast tissues (29). In contrast, we detected substantial downregulation of miR-205 in breast cancer specimens based on our initial profiling. Therefore, we used single miR-205 primer set and probe to confirm the preliminary finding. From a total of 19 pairs of matched breast tumor tissue specimens, average CT (threshold cycle) value for the normal tissue was ~25 whereas the CT value for tumors was ~28 (Fig. 1A). After conversion (30), miR-205 expression level on average was downregulated in breast tumor tissues by ~80% (Fig. 1B) compared to the matched normal tissue. We also examined the miR-205 expression in 9 pairs of matched colon cancer specimens, but found no significant difference in miR-205 expression level between tumors and the matched normal colon tissues (data not shown), suggesting that downregulation of miR-205 may be specific to breast cancer. We then determined miR-205 expression in various breast cancer cell lines along with the non-malignant breast epithelial cell lines MCF-10A. As shown in Fig. 1C, breast cancer cell lines expressed lower levels of miR-205, as compared with MCF-10A cells. These results suggest that miR-205 may function as a tumor suppressor in breast cancer.


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

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

Expression of miR-205 in breast cancer specimens and breast cancer cell linesmiR-205 expression was determined by TaqMan real-time PCR method as described in Materials and Method. Relative CT value (A) or relative expression level of miR-205 (B) in the matched breast tumors and normal breast tissue. C, Relative expression of miR-205 in breast cancer cell lines compared to non-malignant MCF-10A cells from three separate experiments (mean ± SE). **, p < 0.01.
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Related In: Results  -  Collection

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

Figure 1: Expression of miR-205 in breast cancer specimens and breast cancer cell linesmiR-205 expression was determined by TaqMan real-time PCR method as described in Materials and Method. Relative CT value (A) or relative expression level of miR-205 (B) in the matched breast tumors and normal breast tissue. C, Relative expression of miR-205 in breast cancer cell lines compared to non-malignant MCF-10A cells from three separate experiments (mean ± SE). **, p < 0.01.
Mentions: Accumulating evidence indicates that miRNAs can function as oncogenes or tumor suppressors by targeting corresponding tumor suppressor genes or oncogenes (28). To determine the role of miRNAs in breast cancer, we profiled miRNA expression in matched breast tumor specimens by using miRNA TaqMan real-time PCR. We previously showed that the oncogenic miR-21 was more highly expressed in the breast tumors than in the matched normal breast tissues (29). In contrast, we detected substantial downregulation of miR-205 in breast cancer specimens based on our initial profiling. Therefore, we used single miR-205 primer set and probe to confirm the preliminary finding. From a total of 19 pairs of matched breast tumor tissue specimens, average CT (threshold cycle) value for the normal tissue was ~25 whereas the CT value for tumors was ~28 (Fig. 1A). After conversion (30), miR-205 expression level on average was downregulated in breast tumor tissues by ~80% (Fig. 1B) compared to the matched normal tissue. We also examined the miR-205 expression in 9 pairs of matched colon cancer specimens, but found no significant difference in miR-205 expression level between tumors and the matched normal colon tissues (data not shown), suggesting that downregulation of miR-205 may be specific to breast cancer. We then determined miR-205 expression in various breast cancer cell lines along with the non-malignant breast epithelial cell lines MCF-10A. As shown in Fig. 1C, breast cancer cell lines expressed lower levels of miR-205, as compared with MCF-10A cells. These results suggest that miR-205 may function as a tumor suppressor in breast cancer.

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