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Posttranslational Modifications of Rev-Erbα Protein and Abnormal Inflammatory Response in Gastric Cancer
We reported that Rev-erbα, a transcriptional repressor, is reduced in human gastric cancer and that it inhibits glycolysis in cultured gastric cancer cells. However, it is unclear whether Rev-erbα undergoes posttranslational modifications in gastric cancer. Here, we determined levels of Rev-erbα and...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812611/ https://www.ncbi.nlm.nih.gov/pubmed/36618075 http://dx.doi.org/10.1155/2022/6291656 |
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author | Ke, Chen Xiaowen, Cheng Yufeng, Wan Dongchang, Li Huaqing, Zhu Zhengguang, Wang |
author_facet | Ke, Chen Xiaowen, Cheng Yufeng, Wan Dongchang, Li Huaqing, Zhu Zhengguang, Wang |
author_sort | Ke, Chen |
collection | PubMed |
description | We reported that Rev-erbα, a transcriptional repressor, is reduced in human gastric cancer and that it inhibits glycolysis in cultured gastric cancer cells. However, it is unclear whether Rev-erbα undergoes posttranslational modifications in gastric cancer. Here, we determined levels of Rev-erbα and its posttranslational modifications including phosphorylation, SUMOylation, and ubiquitination in N-methyl-N-nitrosourea (MNU)/Helicobacter pylori (H. pylori)-induced gastric cancer in mice and in cultured human gastric cancer cells. Administration of MNU plus H. pylori infection successfully induced gastric tumor in C57BL/6J mice. MNU/H. pylori decreased the levels of Rev-erbα in gastric tumor tissues of mice accompanied by an increase in the level of lactic acid. Rev-erbα protein SUMOylation and ubiquitination modifications were significantly increased, whereas phosphorylation was unchanged, in gastric cancer cells line BGC-823 and MNU/H. pylori-induced mouse gastric cancer tissues. Using human gastric cancer tissues, we found that Rev-erbα was specifically reduced in mucosal epithelial cells in gastric tissue. Cytokine levels were increased in MNU/H. pylori-exposed mice compared with control mice. Similarly, the levels of IL-6 IL-10, TNF-α, and VEGF were higher in the BGC-823 cell line compared with GES-1 cells. IL-6 and IL-1 incubation did not affect Rev-erbα levels in BGC-823 cells. Furthermore, Rev-erbα was recruited on the promoters of these cytokine genes, which suppressed their expression. Conclusively, Rev-erbα SUMOylation and subsequent ubiquitination may contribute to its protein reduction, which leads to increased glycolysis and abnormal inflammatory responses during the development of gastric cancer. Targeting Rev-erbα and its SUMOylation represents promising approaches for prevention and management of gastric cancer. |
format | Online Article Text |
id | pubmed-9812611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-98126112023-01-05 Posttranslational Modifications of Rev-Erbα Protein and Abnormal Inflammatory Response in Gastric Cancer Ke, Chen Xiaowen, Cheng Yufeng, Wan Dongchang, Li Huaqing, Zhu Zhengguang, Wang J Oncol Research Article We reported that Rev-erbα, a transcriptional repressor, is reduced in human gastric cancer and that it inhibits glycolysis in cultured gastric cancer cells. However, it is unclear whether Rev-erbα undergoes posttranslational modifications in gastric cancer. Here, we determined levels of Rev-erbα and its posttranslational modifications including phosphorylation, SUMOylation, and ubiquitination in N-methyl-N-nitrosourea (MNU)/Helicobacter pylori (H. pylori)-induced gastric cancer in mice and in cultured human gastric cancer cells. Administration of MNU plus H. pylori infection successfully induced gastric tumor in C57BL/6J mice. MNU/H. pylori decreased the levels of Rev-erbα in gastric tumor tissues of mice accompanied by an increase in the level of lactic acid. Rev-erbα protein SUMOylation and ubiquitination modifications were significantly increased, whereas phosphorylation was unchanged, in gastric cancer cells line BGC-823 and MNU/H. pylori-induced mouse gastric cancer tissues. Using human gastric cancer tissues, we found that Rev-erbα was specifically reduced in mucosal epithelial cells in gastric tissue. Cytokine levels were increased in MNU/H. pylori-exposed mice compared with control mice. Similarly, the levels of IL-6 IL-10, TNF-α, and VEGF were higher in the BGC-823 cell line compared with GES-1 cells. IL-6 and IL-1 incubation did not affect Rev-erbα levels in BGC-823 cells. Furthermore, Rev-erbα was recruited on the promoters of these cytokine genes, which suppressed their expression. Conclusively, Rev-erbα SUMOylation and subsequent ubiquitination may contribute to its protein reduction, which leads to increased glycolysis and abnormal inflammatory responses during the development of gastric cancer. Targeting Rev-erbα and its SUMOylation represents promising approaches for prevention and management of gastric cancer. Hindawi 2022-12-28 /pmc/articles/PMC9812611/ /pubmed/36618075 http://dx.doi.org/10.1155/2022/6291656 Text en Copyright © 2022 Chen Ke et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Ke, Chen Xiaowen, Cheng Yufeng, Wan Dongchang, Li Huaqing, Zhu Zhengguang, Wang Posttranslational Modifications of Rev-Erbα Protein and Abnormal Inflammatory Response in Gastric Cancer |
title | Posttranslational Modifications of Rev-Erbα Protein and Abnormal Inflammatory Response in Gastric Cancer |
title_full | Posttranslational Modifications of Rev-Erbα Protein and Abnormal Inflammatory Response in Gastric Cancer |
title_fullStr | Posttranslational Modifications of Rev-Erbα Protein and Abnormal Inflammatory Response in Gastric Cancer |
title_full_unstemmed | Posttranslational Modifications of Rev-Erbα Protein and Abnormal Inflammatory Response in Gastric Cancer |
title_short | Posttranslational Modifications of Rev-Erbα Protein and Abnormal Inflammatory Response in Gastric Cancer |
title_sort | posttranslational modifications of rev-erbα protein and abnormal inflammatory response in gastric cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812611/ https://www.ncbi.nlm.nih.gov/pubmed/36618075 http://dx.doi.org/10.1155/2022/6291656 |
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