Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Jun, Zhou, Chao, Li, Junhe, Xiang, Xiaojun, Zhang, Ling, Deng, Jun, Xiong, Jianping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
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
_version_ 1783299705668632576
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
work_keys_str_mv AT chenjun mir215pconfersdoxorubicinresistanceingastriccancercellsbytargetingptenandtimp3
AT zhouchao mir215pconfersdoxorubicinresistanceingastriccancercellsbytargetingptenandtimp3
AT lijunhe mir215pconfersdoxorubicinresistanceingastriccancercellsbytargetingptenandtimp3
AT xiangxiaojun mir215pconfersdoxorubicinresistanceingastriccancercellsbytargetingptenandtimp3
AT zhangling mir215pconfersdoxorubicinresistanceingastriccancercellsbytargetingptenandtimp3
AT dengjun mir215pconfersdoxorubicinresistanceingastriccancercellsbytargetingptenandtimp3
AT xiongjianping mir215pconfersdoxorubicinresistanceingastriccancercellsbytargetingptenandtimp3