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 b...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.展开更多
The purpose of this study was to identify and validate circulating microRNAs （miRNAs） in human plasma for use as breast cancer （BC） biomarkers and to analyze their relationship to clinicopathologic features and it...The purpose of this study was to identify and validate circulating microRNAs （miRNAs） in human plasma for use as breast cancer （BC） biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function. Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis, miR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue （NAT）, whereas let-7b, miR-381, miR-10b, miR-125a-Sp, miR-335, miR-205 and miR-145 were down- regulated greater than two-fold. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls. Using real-time PCR （RT-PCR）, we analyzed miR-205 and miR-155 in archived serum from 30 participants, 20 with breast cancer and I0 healthy people, miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated. Furthermore, we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients. High expression of miR155 was associated with clinical stage, molecular type, Ki-67 and p53 in BC patients （P〈0.05）. By contrast, we found no significant correlation between miR-205 and BC patient clinicopathologic parameters. Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis, miR-205 was down- regulated and miR-155 was up-regulated in BC patient serum, miR-155 was positive correlated with clinical stage and 16-67 and negatively correlated with p53 status.展开更多
文摘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.
基金supported by National Natural Science Foundation of China(No.30872955)
文摘The purpose of this study was to identify and validate circulating microRNAs （miRNAs） in human plasma for use as breast cancer （BC） biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function. Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis, miR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue （NAT）, whereas let-7b, miR-381, miR-10b, miR-125a-Sp, miR-335, miR-205 and miR-145 were down- regulated greater than two-fold. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls. Using real-time PCR （RT-PCR）, we analyzed miR-205 and miR-155 in archived serum from 30 participants, 20 with breast cancer and I0 healthy people, miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated. Furthermore, we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients. High expression of miR155 was associated with clinical stage, molecular type, Ki-67 and p53 in BC patients （P〈0.05）. By contrast, we found no significant correlation between miR-205 and BC patient clinicopathologic parameters. Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis, miR-205 was down- regulated and miR-155 was up-regulated in BC patient serum, miR-155 was positive correlated with clinical stage and 16-67 and negatively correlated with p53 status.
