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MiR-124 targets Slug to regulate epithelial–mesenchymal transition and metastasis of breast cancer
MicroRNAs (miRNAs or miR) have been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. The miR-124 was reported to be attenuated in several tumors, such as glioma, medulloblastoma and hepatocellular carcinoma. However, its role in cancer remains greatly elusive. In t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581604/ https://www.ncbi.nlm.nih.gov/pubmed/23250910 http://dx.doi.org/10.1093/carcin/bgs383 |
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author | Liang, Yong-Jun Wang, Qiu-Yu Zhou, Ci-Xiang Yin, Qian-Qian He, Ming Yu, Xiao-Ting Cao, Dan-Xia Chen, Guo-Qiang He, Jian-Rong Zhao, Qian |
author_facet | Liang, Yong-Jun Wang, Qiu-Yu Zhou, Ci-Xiang Yin, Qian-Qian He, Ming Yu, Xiao-Ting Cao, Dan-Xia Chen, Guo-Qiang He, Jian-Rong Zhao, Qian |
author_sort | Liang, Yong-Jun |
collection | PubMed |
description | MicroRNAs (miRNAs or miR) have been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. The miR-124 was reported to be attenuated in several tumors, such as glioma, medulloblastoma and hepatocellular carcinoma. However, its role in cancer remains greatly elusive. In this study, we show that the miR-124 expression is significantly suppressed in human breast cancer specimens, which is reversely correlated to histological grade of the cancer. More intriguingly, ectopic expression of miR-124 in aggressive breast cancer cell lines MDA-MB-231 and BT-549 strongly inhibits cell motility and invasive capacity, as well as the epithelial–mesenchymal transition process. Also, lentivirus-delivered miR-124 endows MDA-MB-231 cells with the ability to suppress cell colony formation in vitro and pulmonary metastasis in vivo. Further studies have identified the E-cadherin transcription repressor Slug as a direct target gene of miR-124; its downregulation by miR-124 increases the expression of E-cadherin, a hallmark of epithelial cells and a repressor of cell invasion and metastasis. Moreover, knockdown of Slug notably impairs the motility of MDA-MB-231 cells, whereas re-expression of Slug abrogates the reduction of motility and invasion ability induced by miR-124 in MDA-MB-231 cells. These findings highlight an important role for miR-124 in the regulation of invasive and metastatic potential of breast cancer and suggest a potential application of miR-124 in cancer treatment. |
format | Online Article Text |
id | pubmed-3581604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35816042013-02-26 MiR-124 targets Slug to regulate epithelial–mesenchymal transition and metastasis of breast cancer Liang, Yong-Jun Wang, Qiu-Yu Zhou, Ci-Xiang Yin, Qian-Qian He, Ming Yu, Xiao-Ting Cao, Dan-Xia Chen, Guo-Qiang He, Jian-Rong Zhao, Qian Carcinogenesis Original Manuscript MicroRNAs (miRNAs or miR) have been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. The miR-124 was reported to be attenuated in several tumors, such as glioma, medulloblastoma and hepatocellular carcinoma. However, its role in cancer remains greatly elusive. In this study, we show that the miR-124 expression is significantly suppressed in human breast cancer specimens, which is reversely correlated to histological grade of the cancer. More intriguingly, ectopic expression of miR-124 in aggressive breast cancer cell lines MDA-MB-231 and BT-549 strongly inhibits cell motility and invasive capacity, as well as the epithelial–mesenchymal transition process. Also, lentivirus-delivered miR-124 endows MDA-MB-231 cells with the ability to suppress cell colony formation in vitro and pulmonary metastasis in vivo. Further studies have identified the E-cadherin transcription repressor Slug as a direct target gene of miR-124; its downregulation by miR-124 increases the expression of E-cadherin, a hallmark of epithelial cells and a repressor of cell invasion and metastasis. Moreover, knockdown of Slug notably impairs the motility of MDA-MB-231 cells, whereas re-expression of Slug abrogates the reduction of motility and invasion ability induced by miR-124 in MDA-MB-231 cells. These findings highlight an important role for miR-124 in the regulation of invasive and metastatic potential of breast cancer and suggest a potential application of miR-124 in cancer treatment. Oxford University Press 2013-03 2012-12-17 /pmc/articles/PMC3581604/ /pubmed/23250910 http://dx.doi.org/10.1093/carcin/bgs383 Text en © The Author 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. |
spellingShingle | Original Manuscript Liang, Yong-Jun Wang, Qiu-Yu Zhou, Ci-Xiang Yin, Qian-Qian He, Ming Yu, Xiao-Ting Cao, Dan-Xia Chen, Guo-Qiang He, Jian-Rong Zhao, Qian MiR-124 targets Slug to regulate epithelial–mesenchymal transition and metastasis of breast cancer |
title | MiR-124 targets Slug to regulate epithelial–mesenchymal transition and metastasis of breast cancer |
title_full | MiR-124 targets Slug to regulate epithelial–mesenchymal transition and metastasis of breast cancer |
title_fullStr | MiR-124 targets Slug to regulate epithelial–mesenchymal transition and metastasis of breast cancer |
title_full_unstemmed | MiR-124 targets Slug to regulate epithelial–mesenchymal transition and metastasis of breast cancer |
title_short | MiR-124 targets Slug to regulate epithelial–mesenchymal transition and metastasis of breast cancer |
title_sort | mir-124 targets slug to regulate epithelial–mesenchymal transition and metastasis of breast cancer |
topic | Original Manuscript |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581604/ https://www.ncbi.nlm.nih.gov/pubmed/23250910 http://dx.doi.org/10.1093/carcin/bgs383 |
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