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RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer
Forkhead box M1 (FOXM1) plays a critical role in development physiologically and tumorigenesis pathologically. However, insufficient efforts have been dedicated to exploring the regulation, in particular the degradation of FOXM1. Here, the ON-TARGETplus siRNA library targeting E3 ligases was used to...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259508/ https://www.ncbi.nlm.nih.gov/pubmed/37288663 http://dx.doi.org/10.1172/jci.insight.166698 |
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author | Zhang, Shengwei Wang, Jing Hu, Weichao He, Lijiao Tang, Qingyun Li, Jie Jie, Mengmeng Li, Xinzhe Liu, Cheng Ouyang, Qin Yang, Shiming Hu, Changjiang |
author_facet | Zhang, Shengwei Wang, Jing Hu, Weichao He, Lijiao Tang, Qingyun Li, Jie Jie, Mengmeng Li, Xinzhe Liu, Cheng Ouyang, Qin Yang, Shiming Hu, Changjiang |
author_sort | Zhang, Shengwei |
collection | PubMed |
description | Forkhead box M1 (FOXM1) plays a critical role in development physiologically and tumorigenesis pathologically. However, insufficient efforts have been dedicated to exploring the regulation, in particular the degradation of FOXM1. Here, the ON-TARGETplus siRNA library targeting E3 ligases was used to screen potential candidates to repress FOXM1. Of note, mechanism study revealed that RNF112 directly ubiquitinates FOXM1 in gastric cancer, resulting in a decreased FOXM1 transcriptional network and suppressing the proliferation and invasion of gastric cancer. Interestingly, the well-established small-molecule compound RCM-1 significantly enhanced the interaction between RNF112 and FOXM1, which further promoted FOXM1 ubiquitination and subsequently exerted promising anticancer effects in vitro and in vivo. Altogether, we demonstrate that RNF112 suppresses gastric cancer progression by ubiquitinating FOXM1 and highlight the RNF112/FOXM1 axis serves as both prognosis biomarker and therapeutic target in gastric cancer. |
format | Online Article Text |
id | pubmed-10259508 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-102595082023-06-13 RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer Zhang, Shengwei Wang, Jing Hu, Weichao He, Lijiao Tang, Qingyun Li, Jie Jie, Mengmeng Li, Xinzhe Liu, Cheng Ouyang, Qin Yang, Shiming Hu, Changjiang JCI Insight Research Article Forkhead box M1 (FOXM1) plays a critical role in development physiologically and tumorigenesis pathologically. However, insufficient efforts have been dedicated to exploring the regulation, in particular the degradation of FOXM1. Here, the ON-TARGETplus siRNA library targeting E3 ligases was used to screen potential candidates to repress FOXM1. Of note, mechanism study revealed that RNF112 directly ubiquitinates FOXM1 in gastric cancer, resulting in a decreased FOXM1 transcriptional network and suppressing the proliferation and invasion of gastric cancer. Interestingly, the well-established small-molecule compound RCM-1 significantly enhanced the interaction between RNF112 and FOXM1, which further promoted FOXM1 ubiquitination and subsequently exerted promising anticancer effects in vitro and in vivo. Altogether, we demonstrate that RNF112 suppresses gastric cancer progression by ubiquitinating FOXM1 and highlight the RNF112/FOXM1 axis serves as both prognosis biomarker and therapeutic target in gastric cancer. American Society for Clinical Investigation 2023-06-08 /pmc/articles/PMC10259508/ /pubmed/37288663 http://dx.doi.org/10.1172/jci.insight.166698 Text en © 2023 Zhang et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Zhang, Shengwei Wang, Jing Hu, Weichao He, Lijiao Tang, Qingyun Li, Jie Jie, Mengmeng Li, Xinzhe Liu, Cheng Ouyang, Qin Yang, Shiming Hu, Changjiang RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer |
title | RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer |
title_full | RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer |
title_fullStr | RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer |
title_full_unstemmed | RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer |
title_short | RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer |
title_sort | rnf112-mediated foxm1 ubiquitination suppresses the proliferation and invasion of gastric cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259508/ https://www.ncbi.nlm.nih.gov/pubmed/37288663 http://dx.doi.org/10.1172/jci.insight.166698 |
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