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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
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.
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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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