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Ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma

The Ubiquitin-proteasome system (UPS) performs a crucial role in immune activation and tumorigenesis. Nevertheless, the comprehensive role of the ubiquitin-proteasome system in the low-grade glioma (LGG) tumor microenvironment (TME) remains unknown. Ubiquitination modification patterns in LGG patien...

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Autores principales: Gu, Jun, Pang, Lijun, Yan, Donghua, Wang, Chunming, Song, Yuekun, Jin, Zhengshuai, Xu, Zhenwei, Mao, Yuanqing, Liu, Shengzhe, Chen, Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188348/
https://www.ncbi.nlm.nih.gov/pubmed/37053008
http://dx.doi.org/10.18632/aging.204650
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author Gu, Jun
Pang, Lijun
Yan, Donghua
Wang, Chunming
Song, Yuekun
Jin, Zhengshuai
Xu, Zhenwei
Mao, Yuanqing
Liu, Shengzhe
Chen, Sheng
author_facet Gu, Jun
Pang, Lijun
Yan, Donghua
Wang, Chunming
Song, Yuekun
Jin, Zhengshuai
Xu, Zhenwei
Mao, Yuanqing
Liu, Shengzhe
Chen, Sheng
author_sort Gu, Jun
collection PubMed
description The Ubiquitin-proteasome system (UPS) performs a crucial role in immune activation and tumorigenesis. Nevertheless, the comprehensive role of the ubiquitin-proteasome system in the low-grade glioma (LGG) tumor microenvironment (TME) remains unknown. Ubiquitination modification patterns in LGG patients and corresponding characteristics of tumor immune traits, CSC stemness, and cellular senescence were evaluated via a comprehensive analysis of 20 ubiquitination modification regulators. For quantification of the ubiquitination modification status of individual patients, the UM-score was constructed and associated with TME characteristics, clinical features, cancer stem cell stemness, cellular senescence, prognosis, and immunotherapy efficacy. We identified that alterations in multiple ubiquitination regulators are linked to patient survival and the shaping of the tumor microenvironment. We found two different styles of ubiquitination modification in patients with low-grade glioma (immune-inflamed differentiation and immune-exclude dedifferentiation), characterized by high and low UM-score, and the two regulatory patterns of ubiquitination modification on immunity, stemness feature, and cellular senescence. We demonstrate that the UM-score could forecast the subtype of LGG, the immunologic infiltration traits, the biological process, the stemness feature, and the cellular senescence trait. Notably, the UM-score was related to immunotherapeutic efficacy, implying that modifying ubiquitination modification patterns by targeting ubiquitination modification regulators or ubiquitination modification pattern signature genes to reverse unfavorable TME properties will provide new insights into cancer immunotherapy. This research indicated that the ubiquitin-proteasome system is crucial in the formation of TME complexity and multiformity. The UM-score can determine ubiquitination modification status in individual patients, bringing about more personalized and effective immunotherapeutic tactics.
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spelling pubmed-101883482023-05-18 Ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma Gu, Jun Pang, Lijun Yan, Donghua Wang, Chunming Song, Yuekun Jin, Zhengshuai Xu, Zhenwei Mao, Yuanqing Liu, Shengzhe Chen, Sheng Aging (Albany NY) Research Paper The Ubiquitin-proteasome system (UPS) performs a crucial role in immune activation and tumorigenesis. Nevertheless, the comprehensive role of the ubiquitin-proteasome system in the low-grade glioma (LGG) tumor microenvironment (TME) remains unknown. Ubiquitination modification patterns in LGG patients and corresponding characteristics of tumor immune traits, CSC stemness, and cellular senescence were evaluated via a comprehensive analysis of 20 ubiquitination modification regulators. For quantification of the ubiquitination modification status of individual patients, the UM-score was constructed and associated with TME characteristics, clinical features, cancer stem cell stemness, cellular senescence, prognosis, and immunotherapy efficacy. We identified that alterations in multiple ubiquitination regulators are linked to patient survival and the shaping of the tumor microenvironment. We found two different styles of ubiquitination modification in patients with low-grade glioma (immune-inflamed differentiation and immune-exclude dedifferentiation), characterized by high and low UM-score, and the two regulatory patterns of ubiquitination modification on immunity, stemness feature, and cellular senescence. We demonstrate that the UM-score could forecast the subtype of LGG, the immunologic infiltration traits, the biological process, the stemness feature, and the cellular senescence trait. Notably, the UM-score was related to immunotherapeutic efficacy, implying that modifying ubiquitination modification patterns by targeting ubiquitination modification regulators or ubiquitination modification pattern signature genes to reverse unfavorable TME properties will provide new insights into cancer immunotherapy. This research indicated that the ubiquitin-proteasome system is crucial in the formation of TME complexity and multiformity. The UM-score can determine ubiquitination modification status in individual patients, bringing about more personalized and effective immunotherapeutic tactics. Impact Journals 2023-04-11 /pmc/articles/PMC10188348/ /pubmed/37053008 http://dx.doi.org/10.18632/aging.204650 Text en Copyright: © 2023 Gu et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Gu, Jun
Pang, Lijun
Yan, Donghua
Wang, Chunming
Song, Yuekun
Jin, Zhengshuai
Xu, Zhenwei
Mao, Yuanqing
Liu, Shengzhe
Chen, Sheng
Ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma
title Ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma
title_full Ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma
title_fullStr Ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma
title_full_unstemmed Ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma
title_short Ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma
title_sort ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188348/
https://www.ncbi.nlm.nih.gov/pubmed/37053008
http://dx.doi.org/10.18632/aging.204650
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