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miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4
Acquired resistance to chemotherapy is a major obstacle in breast cancer (BC) treatment. Accumulated evidence has uncovered that microRNAs (miRNAs) are vital regulators of chemoresistance in cancer. Growing studies reveal that miR-137 acts as a suppressor in tumor progression. However, it remains ob...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892819/ https://www.ncbi.nlm.nih.gov/pubmed/31801953 http://dx.doi.org/10.1038/s41419-019-2164-2 |
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author | Du, Feiya Yu, Ling Wu, Ying Wang, Shuqian Yao, Jia Zheng, Xiaoxiao Xie, Shangzhi Zhang, Shufeng Lu, Xuemei Liu, Yu Chen, Wei |
author_facet | Du, Feiya Yu, Ling Wu, Ying Wang, Shuqian Yao, Jia Zheng, Xiaoxiao Xie, Shangzhi Zhang, Shufeng Lu, Xuemei Liu, Yu Chen, Wei |
author_sort | Du, Feiya |
collection | PubMed |
description | Acquired resistance to chemotherapy is a major obstacle in breast cancer (BC) treatment. Accumulated evidence has uncovered that microRNAs (miRNAs) are vital regulators of chemoresistance in cancer. Growing studies reveal that miR-137 acts as a suppressor in tumor progression. However, it remains obscure the role of miR-137 in modulating the sensitivity of BC cells to doxorubicin (DOX). In this study, we demonstrate that miR-137 exerts a significant effect on repressing the development of chemoresistance of BC cells in response to DOX via attenuating epithelial-mesenchymal transition (EMT) of tumor cells in vitro and in vivo. MiR-137 overexpression dramatically elevated the sensitivity of BC cells to DOX as well as impaired the DOX-promoted EMT of tumor cells. Mechanistically, miR-137 directly targeted dual-specificity phosphatase 4 (DUSP4) to impact on the EMT and chemoresistance of BC cells upon DOX treatment. Consistently, decreased DUSP4 efficiently enhanced the sensitivity of BC cells to DOX while overexpressed DUSP4 significantly diminished the beneficial effect of miR-137 on BC cells chemoresistance. Moreover, the increased miR-137 heightened the sensitivity of BC cells-derived tumors to DOX through targeting DUSP4 in vivo. Together, our results provide a novel insight into the DOX resistance of BC cells and miR-137 may serve as a new promising therapeutic target for overcoming chemoresistance in BC. |
format | Online Article Text |
id | pubmed-6892819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68928192019-12-05 miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4 Du, Feiya Yu, Ling Wu, Ying Wang, Shuqian Yao, Jia Zheng, Xiaoxiao Xie, Shangzhi Zhang, Shufeng Lu, Xuemei Liu, Yu Chen, Wei Cell Death Dis Article Acquired resistance to chemotherapy is a major obstacle in breast cancer (BC) treatment. Accumulated evidence has uncovered that microRNAs (miRNAs) are vital regulators of chemoresistance in cancer. Growing studies reveal that miR-137 acts as a suppressor in tumor progression. However, it remains obscure the role of miR-137 in modulating the sensitivity of BC cells to doxorubicin (DOX). In this study, we demonstrate that miR-137 exerts a significant effect on repressing the development of chemoresistance of BC cells in response to DOX via attenuating epithelial-mesenchymal transition (EMT) of tumor cells in vitro and in vivo. MiR-137 overexpression dramatically elevated the sensitivity of BC cells to DOX as well as impaired the DOX-promoted EMT of tumor cells. Mechanistically, miR-137 directly targeted dual-specificity phosphatase 4 (DUSP4) to impact on the EMT and chemoresistance of BC cells upon DOX treatment. Consistently, decreased DUSP4 efficiently enhanced the sensitivity of BC cells to DOX while overexpressed DUSP4 significantly diminished the beneficial effect of miR-137 on BC cells chemoresistance. Moreover, the increased miR-137 heightened the sensitivity of BC cells-derived tumors to DOX through targeting DUSP4 in vivo. Together, our results provide a novel insight into the DOX resistance of BC cells and miR-137 may serve as a new promising therapeutic target for overcoming chemoresistance in BC. Nature Publishing Group UK 2019-12-04 /pmc/articles/PMC6892819/ /pubmed/31801953 http://dx.doi.org/10.1038/s41419-019-2164-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Du, Feiya Yu, Ling Wu, Ying Wang, Shuqian Yao, Jia Zheng, Xiaoxiao Xie, Shangzhi Zhang, Shufeng Lu, Xuemei Liu, Yu Chen, Wei miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4 |
title | miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4 |
title_full | miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4 |
title_fullStr | miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4 |
title_full_unstemmed | miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4 |
title_short | miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4 |
title_sort | mir-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting dusp4 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892819/ https://www.ncbi.nlm.nih.gov/pubmed/31801953 http://dx.doi.org/10.1038/s41419-019-2164-2 |
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