Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-β signaling pathway

Therapeutic failure in prostate cancer (PC) is believed to result from its unusually invasive and metastatic nature. Cancer-associated fibroblasts (CAFs) are essential in the tumor microenvironment. We intended to study the role of CAF-derived exosomes in the context of PC and the potential regulato...

Descripción completa

Detalles Bibliográficos
Autores principales: Shan, Guang, Gu, Juan, Zhou, Daoping, Li, Lingxun, Cheng, Wei, Wang, Yueping, Tang, Tian, Wang, Xuedong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080786/
https://www.ncbi.nlm.nih.gov/pubmed/33144675
http://dx.doi.org/10.1038/s12276-020-0431-z
_version_ 1783685509615190016
author Shan, Guang
Gu, Juan
Zhou, Daoping
Li, Lingxun
Cheng, Wei
Wang, Yueping
Tang, Tian
Wang, Xuedong
author_facet Shan, Guang
Gu, Juan
Zhou, Daoping
Li, Lingxun
Cheng, Wei
Wang, Yueping
Tang, Tian
Wang, Xuedong
author_sort Shan, Guang
collection PubMed
description Therapeutic failure in prostate cancer (PC) is believed to result from its unusually invasive and metastatic nature. Cancer-associated fibroblasts (CAFs) are essential in the tumor microenvironment. We intended to study the role of CAF-derived exosomes in the context of PC and the potential regulatory mechanism associated with miR-423-5p and GREM2. CAF-derived exosomes decreased the chemosensitivity of parental PC cells and enhanced the drug resistance of drug-resistant cells. PC-associated fibroblast-derived exosomes carrying miR-423-5p increased the resistance of PC to taxane by inhibiting GREM2 through the TGF-β pathway. Inhibition of the TGF-β pathway partially reversed the increased drug resistance in PC cells induced by CAF-derived exosomes. Inhibition of miR-423-5p enhanced the drug sensitivity of PC cells in vivo. We showed that CAF-secreted exosomal miR-423-5p promoted chemotherapy resistance in PC by targeting GREM2 through the TGF-β pathway. This study may allow the development of novel approaches for PC.
format Online
Article
Text
id pubmed-8080786
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-80807862021-04-29 Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-β signaling pathway Shan, Guang Gu, Juan Zhou, Daoping Li, Lingxun Cheng, Wei Wang, Yueping Tang, Tian Wang, Xuedong Exp Mol Med Article Therapeutic failure in prostate cancer (PC) is believed to result from its unusually invasive and metastatic nature. Cancer-associated fibroblasts (CAFs) are essential in the tumor microenvironment. We intended to study the role of CAF-derived exosomes in the context of PC and the potential regulatory mechanism associated with miR-423-5p and GREM2. CAF-derived exosomes decreased the chemosensitivity of parental PC cells and enhanced the drug resistance of drug-resistant cells. PC-associated fibroblast-derived exosomes carrying miR-423-5p increased the resistance of PC to taxane by inhibiting GREM2 through the TGF-β pathway. Inhibition of the TGF-β pathway partially reversed the increased drug resistance in PC cells induced by CAF-derived exosomes. Inhibition of miR-423-5p enhanced the drug sensitivity of PC cells in vivo. We showed that CAF-secreted exosomal miR-423-5p promoted chemotherapy resistance in PC by targeting GREM2 through the TGF-β pathway. This study may allow the development of novel approaches for PC. Nature Publishing Group UK 2020-11-04 /pmc/articles/PMC8080786/ /pubmed/33144675 http://dx.doi.org/10.1038/s12276-020-0431-z Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Shan, Guang
Gu, Juan
Zhou, Daoping
Li, Lingxun
Cheng, Wei
Wang, Yueping
Tang, Tian
Wang, Xuedong
Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-β signaling pathway
title Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-β signaling pathway
title_full Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-β signaling pathway
title_fullStr Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-β signaling pathway
title_full_unstemmed Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-β signaling pathway
title_short Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-β signaling pathway
title_sort cancer-associated fibroblast-secreted exosomal mir-423-5p promotes chemotherapy resistance in prostate cancer by targeting grem2 through the tgf-β signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080786/
https://www.ncbi.nlm.nih.gov/pubmed/33144675
http://dx.doi.org/10.1038/s12276-020-0431-z
work_keys_str_mv AT shanguang cancerassociatedfibroblastsecretedexosomalmir4235ppromoteschemotherapyresistanceinprostatecancerbytargetinggrem2throughthetgfbsignalingpathway
AT gujuan cancerassociatedfibroblastsecretedexosomalmir4235ppromoteschemotherapyresistanceinprostatecancerbytargetinggrem2throughthetgfbsignalingpathway
AT zhoudaoping cancerassociatedfibroblastsecretedexosomalmir4235ppromoteschemotherapyresistanceinprostatecancerbytargetinggrem2throughthetgfbsignalingpathway
AT lilingxun cancerassociatedfibroblastsecretedexosomalmir4235ppromoteschemotherapyresistanceinprostatecancerbytargetinggrem2throughthetgfbsignalingpathway
AT chengwei cancerassociatedfibroblastsecretedexosomalmir4235ppromoteschemotherapyresistanceinprostatecancerbytargetinggrem2throughthetgfbsignalingpathway
AT wangyueping cancerassociatedfibroblastsecretedexosomalmir4235ppromoteschemotherapyresistanceinprostatecancerbytargetinggrem2throughthetgfbsignalingpathway
AT tangtian cancerassociatedfibroblastsecretedexosomalmir4235ppromoteschemotherapyresistanceinprostatecancerbytargetinggrem2throughthetgfbsignalingpathway
AT wangxuedong cancerassociatedfibroblastsecretedexosomalmir4235ppromoteschemotherapyresistanceinprostatecancerbytargetinggrem2throughthetgfbsignalingpathway

Ejemplares similares