LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance

The refractory of castration-resistant prostate cancer (CRPC) is mainly reflected in drug resistance. The current research on the resistance mechanism of CRPC is still in its infancy. In this study, we revealed for the first time the key role of LncRNA PCBP1-AS1 in CRPC drug resistance. Through deta...

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Autores principales: Zhang, Boya, Zhang, Mingpeng, Shen, Chunyi, Liu, Guancong, Zhang, Fan, Hou, Jingyu, Yao, Weitao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452729/
https://www.ncbi.nlm.nih.gov/pubmed/34545063
http://dx.doi.org/10.1038/s41419-021-04144-2
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author Zhang, Boya
Zhang, Mingpeng
Shen, Chunyi
Liu, Guancong
Zhang, Fan
Hou, Jingyu
Yao, Weitao
author_facet Zhang, Boya
Zhang, Mingpeng
Shen, Chunyi
Liu, Guancong
Zhang, Fan
Hou, Jingyu
Yao, Weitao
author_sort Zhang, Boya
collection PubMed
description The refractory of castration-resistant prostate cancer (CRPC) is mainly reflected in drug resistance. The current research on the resistance mechanism of CRPC is still in its infancy. In this study, we revealed for the first time the key role of LncRNA PCBP1-AS1 in CRPC drug resistance. Through detailed in vivo and in vitro studies, we found that PCBP1-AS1 may enhance the deubiquitination of AR/AR-V7 by stabilizing the USP22-AR/AR-V7 complex, thereby preventing AR/AR-V7 from being degraded through the ubiquitin–proteasome pathway. Targeting PCBP1-AS1 can significantly restore the drug sensitivity of enzalutamide-resistant tumors in vivo and in vitro. Our research further expands the function of LncRNA in castration-resistant prostate cancer, which may provide new potential for clinical diagnosis and targeted therapy.
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spelling pubmed-84527292021-10-05 LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance Zhang, Boya Zhang, Mingpeng Shen, Chunyi Liu, Guancong Zhang, Fan Hou, Jingyu Yao, Weitao Cell Death Dis Article The refractory of castration-resistant prostate cancer (CRPC) is mainly reflected in drug resistance. The current research on the resistance mechanism of CRPC is still in its infancy. In this study, we revealed for the first time the key role of LncRNA PCBP1-AS1 in CRPC drug resistance. Through detailed in vivo and in vitro studies, we found that PCBP1-AS1 may enhance the deubiquitination of AR/AR-V7 by stabilizing the USP22-AR/AR-V7 complex, thereby preventing AR/AR-V7 from being degraded through the ubiquitin–proteasome pathway. Targeting PCBP1-AS1 can significantly restore the drug sensitivity of enzalutamide-resistant tumors in vivo and in vitro. Our research further expands the function of LncRNA in castration-resistant prostate cancer, which may provide new potential for clinical diagnosis and targeted therapy. Nature Publishing Group UK 2021-09-20 /pmc/articles/PMC8452729/ /pubmed/34545063 http://dx.doi.org/10.1038/s41419-021-04144-2 Text en © The Author(s) 2021 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
Zhang, Boya
Zhang, Mingpeng
Shen, Chunyi
Liu, Guancong
Zhang, Fan
Hou, Jingyu
Yao, Weitao
LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance
title LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance
title_full LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance
title_fullStr LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance
title_full_unstemmed LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance
title_short LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance
title_sort lncrna pcbp1-as1-mediated ar/ar-v7 deubiquitination enhances prostate cancer enzalutamide resistance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452729/
https://www.ncbi.nlm.nih.gov/pubmed/34545063
http://dx.doi.org/10.1038/s41419-021-04144-2
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