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Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway
BACKGROUND: The dysfunction of myc-related zinc finger protein (MAZ) has been proven to contribute to tumorigenesis and development of multiple cancer types. However, the biological roles and clinical significance of MAZ in clear cell renal carcinoma (ccRCC) remain unclear. METHODS: MAZ expression w...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240279/ https://www.ncbi.nlm.nih.gov/pubmed/34183010 http://dx.doi.org/10.1186/s12935-021-02020-9 |
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author | Ren, Li-Xin Qi, Jin-Chun Zhao, An-Ning Shi, Bei Zhang, Hong Wang, Dan-Dan Yang, Zhan |
author_facet | Ren, Li-Xin Qi, Jin-Chun Zhao, An-Ning Shi, Bei Zhang, Hong Wang, Dan-Dan Yang, Zhan |
author_sort | Ren, Li-Xin |
collection | PubMed |
description | BACKGROUND: The dysfunction of myc-related zinc finger protein (MAZ) has been proven to contribute to tumorigenesis and development of multiple cancer types. However, the biological roles and clinical significance of MAZ in clear cell renal carcinoma (ccRCC) remain unclear. METHODS: MAZ expression was examined in ccRCC and normal kidney tissue by quantitative real-time PCR and Western blot. Statistical analysis was used to evaluate the clinical correlation between MAZ expression and clinicopathological characteristics to determine the relationship between MAZ expression and the survival of ccRCC patients. The biological roles of MAZ in cells were investigated in vitro using MTT and colony assays. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to investigate the relationship between MAZ and its potential downstream signaling molecules. RESULTS: MAZ expression is elevated in ccRCC tissues, and higher levels of MAZ were correlated with poor survival of patients with ccRCC. MAZ upregulation elevates the proliferation ability of ccRCC cells in vitro, whereas silencing MAZ represses this ability. Our results further reveal that MAZ promotes cell growth, which is dependent on ERK signaling. Importantly, we found that MAZ positively regulates MAP2K2 expression in ccRCC cells. Mechanistically, MAZ binds to the MAP2K2 promoter and increases MAP2K2 transcription. Furthermore, MAP2K2 levels were shown to be increased in ccRCC tissues and to be associated with a poor prognosis of ccRCC patients. MAP2K2 upregulation activates the ERK signaling pathway and promotes ccRCC progression. CONCLUSION: These results reveal that the MAZ/MAP2K2/ERK signaling axis plays a crucial role in promoting ccRCC progression, which suggests the potential therapeutic utility of MAZ in ccRCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02020-9. |
format | Online Article Text |
id | pubmed-8240279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-82402792021-06-29 Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway Ren, Li-Xin Qi, Jin-Chun Zhao, An-Ning Shi, Bei Zhang, Hong Wang, Dan-Dan Yang, Zhan Cancer Cell Int Primary Research BACKGROUND: The dysfunction of myc-related zinc finger protein (MAZ) has been proven to contribute to tumorigenesis and development of multiple cancer types. However, the biological roles and clinical significance of MAZ in clear cell renal carcinoma (ccRCC) remain unclear. METHODS: MAZ expression was examined in ccRCC and normal kidney tissue by quantitative real-time PCR and Western blot. Statistical analysis was used to evaluate the clinical correlation between MAZ expression and clinicopathological characteristics to determine the relationship between MAZ expression and the survival of ccRCC patients. The biological roles of MAZ in cells were investigated in vitro using MTT and colony assays. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to investigate the relationship between MAZ and its potential downstream signaling molecules. RESULTS: MAZ expression is elevated in ccRCC tissues, and higher levels of MAZ were correlated with poor survival of patients with ccRCC. MAZ upregulation elevates the proliferation ability of ccRCC cells in vitro, whereas silencing MAZ represses this ability. Our results further reveal that MAZ promotes cell growth, which is dependent on ERK signaling. Importantly, we found that MAZ positively regulates MAP2K2 expression in ccRCC cells. Mechanistically, MAZ binds to the MAP2K2 promoter and increases MAP2K2 transcription. Furthermore, MAP2K2 levels were shown to be increased in ccRCC tissues and to be associated with a poor prognosis of ccRCC patients. MAP2K2 upregulation activates the ERK signaling pathway and promotes ccRCC progression. CONCLUSION: These results reveal that the MAZ/MAP2K2/ERK signaling axis plays a crucial role in promoting ccRCC progression, which suggests the potential therapeutic utility of MAZ in ccRCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02020-9. BioMed Central 2021-06-28 /pmc/articles/PMC8240279/ /pubmed/34183010 http://dx.doi.org/10.1186/s12935-021-02020-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Ren, Li-Xin Qi, Jin-Chun Zhao, An-Ning Shi, Bei Zhang, Hong Wang, Dan-Dan Yang, Zhan Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway |
title | Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway |
title_full | Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway |
title_fullStr | Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway |
title_full_unstemmed | Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway |
title_short | Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway |
title_sort | myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the map2k2-dependent erk pathway |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240279/ https://www.ncbi.nlm.nih.gov/pubmed/34183010 http://dx.doi.org/10.1186/s12935-021-02020-9 |
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