MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer
The epithelial-to-mesenchymal (EMT) transition is a prerequisite for conferring metastatic potential during tumor progression. microRNA-30a (miR-30a) expression was significantly lower in aggressive breast cancer cell lines compared with non-invasive breast cancer and non-malignant mammary epithelia...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941328/ https://www.ncbi.nlm.nih.gov/pubmed/26918943 http://dx.doi.org/10.18632/oncotarget.7656 |
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author | Chang, Chia-Wei Yu, Jyh-Cherng Hsieh, Yi-Hsien Yao, Chung-Chin Chao, Jui-I Chen, Po-Ming Hsieh, Hsiao-Yen Hsiung, Chia-Ni Chu, Hou-Wei Shen, Chen-Yang Cheng, Chun-Wen |
author_facet | Chang, Chia-Wei Yu, Jyh-Cherng Hsieh, Yi-Hsien Yao, Chung-Chin Chao, Jui-I Chen, Po-Ming Hsieh, Hsiao-Yen Hsiung, Chia-Ni Chu, Hou-Wei Shen, Chen-Yang Cheng, Chun-Wen |
author_sort | Chang, Chia-Wei |
collection | PubMed |
description | The epithelial-to-mesenchymal (EMT) transition is a prerequisite for conferring metastatic potential during tumor progression. microRNA-30a (miR-30a) expression was significantly lower in aggressive breast cancer cell lines compared with non-invasive breast cancer and non-malignant mammary epithelial cell lines. In contrast, miR-30a overexpression reversed the mesenchymal appearance of cancer cells to result in a cobblestone-like epithelial phenotype. We identified Slug, one of the master regulators of EMT, as a target of miR-30a using in silico prediction. Reporter assays indicated that miR-30a could bind to the 3′-untranslted region of Slug mRNA. Furthermore, we linked miR-30a to increased expression of claudins, a family of tight junction transmembrane proteins. An interaction between Slug and E-box in the claudin promoter sequences was reduced upon miR-30a overexpression, further leading to reduction of filopodia formation and decreased invasiveness/metastasis capabilities of breast cancer cells. Consistently, delivery of miR-30a in xenografted mice decreased tumor invasion and migration. In patients with breast cancer, a significantly elevated risk of the miR-30a(low)/CLDN2(low)/FSCN(high) genotype was observed, linking to a phenotypic manifestation of larger tumor size, lymph node metastasis, and advanced tumor stage among patients. In conclusion, the miR-30a/Slug axis inhibits mesenchymal tumor development by interfering with metastatic cancer cell programming and may be a potential target for therapy in breast cancer. |
format | Online Article Text |
id | pubmed-4941328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49413282016-07-19 MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer Chang, Chia-Wei Yu, Jyh-Cherng Hsieh, Yi-Hsien Yao, Chung-Chin Chao, Jui-I Chen, Po-Ming Hsieh, Hsiao-Yen Hsiung, Chia-Ni Chu, Hou-Wei Shen, Chen-Yang Cheng, Chun-Wen Oncotarget Research Paper The epithelial-to-mesenchymal (EMT) transition is a prerequisite for conferring metastatic potential during tumor progression. microRNA-30a (miR-30a) expression was significantly lower in aggressive breast cancer cell lines compared with non-invasive breast cancer and non-malignant mammary epithelial cell lines. In contrast, miR-30a overexpression reversed the mesenchymal appearance of cancer cells to result in a cobblestone-like epithelial phenotype. We identified Slug, one of the master regulators of EMT, as a target of miR-30a using in silico prediction. Reporter assays indicated that miR-30a could bind to the 3′-untranslted region of Slug mRNA. Furthermore, we linked miR-30a to increased expression of claudins, a family of tight junction transmembrane proteins. An interaction between Slug and E-box in the claudin promoter sequences was reduced upon miR-30a overexpression, further leading to reduction of filopodia formation and decreased invasiveness/metastasis capabilities of breast cancer cells. Consistently, delivery of miR-30a in xenografted mice decreased tumor invasion and migration. In patients with breast cancer, a significantly elevated risk of the miR-30a(low)/CLDN2(low)/FSCN(high) genotype was observed, linking to a phenotypic manifestation of larger tumor size, lymph node metastasis, and advanced tumor stage among patients. In conclusion, the miR-30a/Slug axis inhibits mesenchymal tumor development by interfering with metastatic cancer cell programming and may be a potential target for therapy in breast cancer. Impact Journals LLC 2016-02-24 /pmc/articles/PMC4941328/ /pubmed/26918943 http://dx.doi.org/10.18632/oncotarget.7656 Text en Copyright: © 2016 Chang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Chang, Chia-Wei Yu, Jyh-Cherng Hsieh, Yi-Hsien Yao, Chung-Chin Chao, Jui-I Chen, Po-Ming Hsieh, Hsiao-Yen Hsiung, Chia-Ni Chu, Hou-Wei Shen, Chen-Yang Cheng, Chun-Wen MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer |
title | MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer |
title_full | MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer |
title_fullStr | MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer |
title_full_unstemmed | MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer |
title_short | MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer |
title_sort | microrna-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting slug in breast cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941328/ https://www.ncbi.nlm.nih.gov/pubmed/26918943 http://dx.doi.org/10.18632/oncotarget.7656 |
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