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Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer deaths due to its highly aggressive biological nature and resistance to chemotherapy. Previous studies indicate that miR-21 is an important regulator in the activation of cancer-associated fibroblasts (CAFs). However, whe...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cognizant Communication Corporation
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844724/ https://www.ncbi.nlm.nih.gov/pubmed/28477403 http://dx.doi.org/10.3727/096504017X14934840662335 |
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author | Zhang, Lulin Yao, Jun Li, Wenyao Zhang, Ce |
author_facet | Zhang, Lulin Yao, Jun Li, Wenyao Zhang, Ce |
author_sort | Zhang, Lulin |
collection | PubMed |
description | Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer deaths due to its highly aggressive biological nature and resistance to chemotherapy. Previous studies indicate that miR-21 is an important regulator in the activation of cancer-associated fibroblasts (CAFs). However, whether miR-21 in CAFs would regulate PDAC’s tumor microenvironment and lead to drug resistance remain unknown. In this study, we evaluated the relationship between CAF activation, miR-21 expression, and drug resistance using tumor samples from PDAC patients. We changed the miR-21 expression level in CAFs and tested its roles in regulating the function of CAFs. In addition, we explored the roles of miR-21 in CAFs in the development of PDAC using an animal model. We found that PDAC patients who were resistant to gemcitabine treatment tended to have higher miR-21 expression and more activated CAFs. An in vitro study showed that CAFs with high miR-21 expression had elevated MMP-3, MMP-9, PDGF, and CCL-7 expression and promoted the invasion of PDAC cell lines. miR-21 overexpression also contributed to the activation of CAFs by regulating the PDCD4 gene. The in vivo study showed that upregulating miR-21 in CAFs promoted PDAC desmoplasia and increased its drug resistance to gemcitabine treatment, but downregulating miR-21 in CAFs suppressed desmoplasia and enhanced the effect of gemcitabine. We concluded that miR-21 promoted the activation of CAFs and contributed to the drug resistance of PDAC. |
format | Online Article Text |
id | pubmed-7844724 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cognizant Communication Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-78447242021-02-16 Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer Zhang, Lulin Yao, Jun Li, Wenyao Zhang, Ce Oncol Res Article Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer deaths due to its highly aggressive biological nature and resistance to chemotherapy. Previous studies indicate that miR-21 is an important regulator in the activation of cancer-associated fibroblasts (CAFs). However, whether miR-21 in CAFs would regulate PDAC’s tumor microenvironment and lead to drug resistance remain unknown. In this study, we evaluated the relationship between CAF activation, miR-21 expression, and drug resistance using tumor samples from PDAC patients. We changed the miR-21 expression level in CAFs and tested its roles in regulating the function of CAFs. In addition, we explored the roles of miR-21 in CAFs in the development of PDAC using an animal model. We found that PDAC patients who were resistant to gemcitabine treatment tended to have higher miR-21 expression and more activated CAFs. An in vitro study showed that CAFs with high miR-21 expression had elevated MMP-3, MMP-9, PDGF, and CCL-7 expression and promoted the invasion of PDAC cell lines. miR-21 overexpression also contributed to the activation of CAFs by regulating the PDCD4 gene. The in vivo study showed that upregulating miR-21 in CAFs promoted PDAC desmoplasia and increased its drug resistance to gemcitabine treatment, but downregulating miR-21 in CAFs suppressed desmoplasia and enhanced the effect of gemcitabine. We concluded that miR-21 promoted the activation of CAFs and contributed to the drug resistance of PDAC. Cognizant Communication Corporation 2018-07-05 /pmc/articles/PMC7844724/ /pubmed/28477403 http://dx.doi.org/10.3727/096504017X14934840662335 Text en Copyright © 2018 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License. |
spellingShingle | Article Zhang, Lulin Yao, Jun Li, Wenyao Zhang, Ce Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer |
title | Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer |
title_full | Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer |
title_fullStr | Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer |
title_full_unstemmed | Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer |
title_short | Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer |
title_sort | micro-rna-21 regulates cancer-associated fibroblast-mediated drug resistance in pancreatic cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844724/ https://www.ncbi.nlm.nih.gov/pubmed/28477403 http://dx.doi.org/10.3727/096504017X14934840662335 |
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