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Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis
The mutual interplay between epigenetic modifications and metabolic rewiring contributes to malignant features of prostate adenocarcinoma (PRAD). This study aimed to uncover the biological roles of deubiquitylase USP35 in PRAD and find effective epigenetic or metabolic targets. Bioinformatic tools o...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649703/ https://www.ncbi.nlm.nih.gov/pubmed/36357379 http://dx.doi.org/10.1038/s41420-022-01231-x |
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author | Lin, Guowen Huang, Tianrun Zhang, Xiaobo Wang, Gangmin |
author_facet | Lin, Guowen Huang, Tianrun Zhang, Xiaobo Wang, Gangmin |
author_sort | Lin, Guowen |
collection | PubMed |
description | The mutual interplay between epigenetic modifications and metabolic rewiring contributes to malignant features of prostate adenocarcinoma (PRAD). This study aimed to uncover the biological roles of deubiquitylase USP35 in PRAD and find effective epigenetic or metabolic targets. Bioinformatic tools or methods revealed that USP35 is upregulated in PRAD samples and correlates with inferior prognosis. The in vitro and in vivo assays suggested that USP35 could enhance malignant features of PRAD cells. Mechanistically, we found that USP35 could directly deubiquitinate and stabilize BRPF1 proteins. USP35 depends on accumulated BRPF1 proteins to accelerate cell growth, stem-like properties, and migration in vitro and in vivo. Interestingly, high BRPF1 could bind to promoter of SREBP2 and activate the SREBP2 transcriptional capacity. Therefore, USP35/BRPF1 aixs could promote expressions of mevalonate (MVA) metabolism signature in a SREBP2-dependent manner. USP35 depends on BRPF1 to maintain the activity of mevalonate metabolism in PRAD cells. Last of all, we observed that targeting BRPF1 or using MVA inhibitor (atorvastatin) are effective to suppress USP35(high) PRAD in vivo tumor growth. USP35 is an indicator of MVA metabolic signature in PRAD. Collectively, our study highlighted the USP35/BRPF1/SREBP2 axis in modulating MVA metabolism in PRAD, suggesting the significance of BRPF1 or MVA as the potential therapeutic targets for PRAD treatment. |
format | Online Article Text |
id | pubmed-9649703 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96497032022-11-15 Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis Lin, Guowen Huang, Tianrun Zhang, Xiaobo Wang, Gangmin Cell Death Discov Article The mutual interplay between epigenetic modifications and metabolic rewiring contributes to malignant features of prostate adenocarcinoma (PRAD). This study aimed to uncover the biological roles of deubiquitylase USP35 in PRAD and find effective epigenetic or metabolic targets. Bioinformatic tools or methods revealed that USP35 is upregulated in PRAD samples and correlates with inferior prognosis. The in vitro and in vivo assays suggested that USP35 could enhance malignant features of PRAD cells. Mechanistically, we found that USP35 could directly deubiquitinate and stabilize BRPF1 proteins. USP35 depends on accumulated BRPF1 proteins to accelerate cell growth, stem-like properties, and migration in vitro and in vivo. Interestingly, high BRPF1 could bind to promoter of SREBP2 and activate the SREBP2 transcriptional capacity. Therefore, USP35/BRPF1 aixs could promote expressions of mevalonate (MVA) metabolism signature in a SREBP2-dependent manner. USP35 depends on BRPF1 to maintain the activity of mevalonate metabolism in PRAD cells. Last of all, we observed that targeting BRPF1 or using MVA inhibitor (atorvastatin) are effective to suppress USP35(high) PRAD in vivo tumor growth. USP35 is an indicator of MVA metabolic signature in PRAD. Collectively, our study highlighted the USP35/BRPF1/SREBP2 axis in modulating MVA metabolism in PRAD, suggesting the significance of BRPF1 or MVA as the potential therapeutic targets for PRAD treatment. Nature Publishing Group UK 2022-11-10 /pmc/articles/PMC9649703/ /pubmed/36357379 http://dx.doi.org/10.1038/s41420-022-01231-x Text en © The Author(s) 2022 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 Lin, Guowen Huang, Tianrun Zhang, Xiaobo Wang, Gangmin Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis |
title | Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis |
title_full | Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis |
title_fullStr | Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis |
title_full_unstemmed | Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis |
title_short | Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis |
title_sort | deubiquitinase usp35 stabilizes brpf1 to activate mevalonate (mva) metabolism during prostate tumorigenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649703/ https://www.ncbi.nlm.nih.gov/pubmed/36357379 http://dx.doi.org/10.1038/s41420-022-01231-x |
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