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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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.
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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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