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High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells

Clear cell renal cell carcinoma (ccRCC) is a frequently occurring renal cancer. The Von Hippel-Lindau disease tumor suppressor VHL, a known tumor suppressor gene, is frequently mutated in about 50% of patients with ccRCC. However, it is unclear whether VHL influences the progression of ccRCC tumors...

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Autores principales: Zhu, Songbiao, Ding, Wenxi, Chen, Yuling, Wang, Weixuan, Xu, Renhua, Liu, Chongdong, Liu, Xiaohui, Deng, Haiteng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880812/
https://www.ncbi.nlm.nih.gov/pubmed/33647481
http://dx.doi.org/10.1016/j.gpb.2019.12.002
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author Zhu, Songbiao
Ding, Wenxi
Chen, Yuling
Wang, Weixuan
Xu, Renhua
Liu, Chongdong
Liu, Xiaohui
Deng, Haiteng
author_facet Zhu, Songbiao
Ding, Wenxi
Chen, Yuling
Wang, Weixuan
Xu, Renhua
Liu, Chongdong
Liu, Xiaohui
Deng, Haiteng
author_sort Zhu, Songbiao
collection PubMed
description Clear cell renal cell carcinoma (ccRCC) is a frequently occurring renal cancer. The Von Hippel-Lindau disease tumor suppressor VHL, a known tumor suppressor gene, is frequently mutated in about 50% of patients with ccRCC. However, it is unclear whether VHL influences the progression of ccRCC tumors expressing wild-type VHL. In the present study, we found that higher expression of VHL was correlated with the better disease-free survival (DFS) in ccRCC patients using The Cancer Genome Atlas (TCGA) datasets. We revealed that VHL overexpression in ccRCC cells inhibited epithelial-mesenchymal transition (EMT), sterol regulatory element-binding protein 1 (SREBP1)-regulated triglyceride synthesis, and cell proliferation. Proteomic analysis provided us a global view that VHL regulated four biological processes, including metabolism, immune regulation, apoptosis, and cell movement. Importantly, we found that VHL overexpression led to up-regulated expression of proteins associated with antigen processing and interferon-responsive proteins, thus rendering ccRCC cells more sensitive to interferon treatment. We defined an interferon-responsive signature (IRS) composed of ten interferon-responsive proteins, whose mRNA expression levels were positively correlated with DFS in ccRCC patients. Taken together, our results propose that the subset of ccRCC patients with high VHL expression benefit from immunotherapy.
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spelling pubmed-98808122023-01-28 High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells Zhu, Songbiao Ding, Wenxi Chen, Yuling Wang, Weixuan Xu, Renhua Liu, Chongdong Liu, Xiaohui Deng, Haiteng Genomics Proteomics Bioinformatics Original Research Clear cell renal cell carcinoma (ccRCC) is a frequently occurring renal cancer. The Von Hippel-Lindau disease tumor suppressor VHL, a known tumor suppressor gene, is frequently mutated in about 50% of patients with ccRCC. However, it is unclear whether VHL influences the progression of ccRCC tumors expressing wild-type VHL. In the present study, we found that higher expression of VHL was correlated with the better disease-free survival (DFS) in ccRCC patients using The Cancer Genome Atlas (TCGA) datasets. We revealed that VHL overexpression in ccRCC cells inhibited epithelial-mesenchymal transition (EMT), sterol regulatory element-binding protein 1 (SREBP1)-regulated triglyceride synthesis, and cell proliferation. Proteomic analysis provided us a global view that VHL regulated four biological processes, including metabolism, immune regulation, apoptosis, and cell movement. Importantly, we found that VHL overexpression led to up-regulated expression of proteins associated with antigen processing and interferon-responsive proteins, thus rendering ccRCC cells more sensitive to interferon treatment. We defined an interferon-responsive signature (IRS) composed of ten interferon-responsive proteins, whose mRNA expression levels were positively correlated with DFS in ccRCC patients. Taken together, our results propose that the subset of ccRCC patients with high VHL expression benefit from immunotherapy. Elsevier 2022-08 2021-02-27 /pmc/articles/PMC9880812/ /pubmed/33647481 http://dx.doi.org/10.1016/j.gpb.2019.12.002 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Zhu, Songbiao
Ding, Wenxi
Chen, Yuling
Wang, Weixuan
Xu, Renhua
Liu, Chongdong
Liu, Xiaohui
Deng, Haiteng
High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells
title High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells
title_full High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells
title_fullStr High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells
title_full_unstemmed High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells
title_short High VHL Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells
title_sort high vhl expression reverses warburg phenotype and enhances immunogenicity in kidney tumor cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880812/
https://www.ncbi.nlm.nih.gov/pubmed/33647481
http://dx.doi.org/10.1016/j.gpb.2019.12.002
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