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miR-21-5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3
Drug resistance and disease recurrence are major obstacles to the effective treatment of cancer, including gastric cancer (GC). However, the mechanisms of drug resistance remain to be fully elucidated. The present study investigated the roles of microRNA (miR)-21-5p in the doxorubicin (DOX) resistan...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810196/ https://www.ncbi.nlm.nih.gov/pubmed/29393355 http://dx.doi.org/10.3892/ijmm.2018.3405 |
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author | Chen, Jun Zhou, Chao Li, Junhe Xiang, Xiaojun Zhang, Ling Deng, Jun Xiong, Jianping |
author_facet | Chen, Jun Zhou, Chao Li, Junhe Xiang, Xiaojun Zhang, Ling Deng, Jun Xiong, Jianping |
author_sort | Chen, Jun |
collection | PubMed |
description | Drug resistance and disease recurrence are major obstacles to the effective treatment of cancer, including gastric cancer (GC). However, the mechanisms of drug resistance remain to be fully elucidated. The present study investigated the roles of microRNA (miR)-21-5p in the doxorubicin (DOX) resistance of GC cells and the underlying mechanisms. miR-21-5p expression levels were identified to be inversely correlated with two well-known tumor suppressor genes, phosphatase and tensin homologue and tissue inhibitor of matrix metalloproteinases 3, and were upregulated in GC cell lines in proportion to their degree of resistance. Suppressing miR-21-5p expression partially sensitized SGC7901/DOX cells to DOX, suggesting that knockdown of miR-21-5p expression may be used as a therapeutic strategy to improve GC cell resistance. Importantly, increased miR-21-5p expression levels at diagnosis were correlated with clinicopathological characteristics including advanced stage and poor prognosis, further implying that a relapse of GC may be a consequence of miR-21-5p upregulation, thus providing evidence for the potential utility of miR-21-5p antagonism to sensitize GC cells to DOX chemotherapy. |
format | Online Article Text |
id | pubmed-5810196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-58101962018-02-27 miR-21-5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3 Chen, Jun Zhou, Chao Li, Junhe Xiang, Xiaojun Zhang, Ling Deng, Jun Xiong, Jianping Int J Mol Med Articles Drug resistance and disease recurrence are major obstacles to the effective treatment of cancer, including gastric cancer (GC). However, the mechanisms of drug resistance remain to be fully elucidated. The present study investigated the roles of microRNA (miR)-21-5p in the doxorubicin (DOX) resistance of GC cells and the underlying mechanisms. miR-21-5p expression levels were identified to be inversely correlated with two well-known tumor suppressor genes, phosphatase and tensin homologue and tissue inhibitor of matrix metalloproteinases 3, and were upregulated in GC cell lines in proportion to their degree of resistance. Suppressing miR-21-5p expression partially sensitized SGC7901/DOX cells to DOX, suggesting that knockdown of miR-21-5p expression may be used as a therapeutic strategy to improve GC cell resistance. Importantly, increased miR-21-5p expression levels at diagnosis were correlated with clinicopathological characteristics including advanced stage and poor prognosis, further implying that a relapse of GC may be a consequence of miR-21-5p upregulation, thus providing evidence for the potential utility of miR-21-5p antagonism to sensitize GC cells to DOX chemotherapy. D.A. Spandidos 2018-04 2018-01-18 /pmc/articles/PMC5810196/ /pubmed/29393355 http://dx.doi.org/10.3892/ijmm.2018.3405 Text en Copyright: © Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Chen, Jun Zhou, Chao Li, Junhe Xiang, Xiaojun Zhang, Ling Deng, Jun Xiong, Jianping miR-21-5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3 |
title | miR-21-5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3 |
title_full | miR-21-5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3 |
title_fullStr | miR-21-5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3 |
title_full_unstemmed | miR-21-5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3 |
title_short | miR-21-5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3 |
title_sort | mir-21-5p confers doxorubicin resistance in gastric cancer cells by targeting pten and timp3 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810196/ https://www.ncbi.nlm.nih.gov/pubmed/29393355 http://dx.doi.org/10.3892/ijmm.2018.3405 |
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