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BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer

BRD7 functions as a crucial tumor suppressor in numerous malignancies. However, the effects of BRD7 on colorectal cancer (CRC) progression are still unknown. Here, based on the BRD7 knockout (BRD7(–/–)) and BRD7(flox/flox) (BRD7(+/+)) mouse models constructed in our previous work, we established an...

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Autores principales: Zhao, Ran, Liu, Yukun, Wu, Chunchun, Li, Mengna, Wei, Yanmei, Niu, Weihong, Yang, Jing, Fan, Songqing, Xie, Yong, Li, Hui, Wang, Wei, Zeng, Zhaoyang, Xiong, Wei, Li, Xiaoling, Li, Guiyuan, Zhou, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181413/
https://www.ncbi.nlm.nih.gov/pubmed/34109174
http://dx.doi.org/10.3389/fcell.2021.659392
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author Zhao, Ran
Liu, Yukun
Wu, Chunchun
Li, Mengna
Wei, Yanmei
Niu, Weihong
Yang, Jing
Fan, Songqing
Xie, Yong
Li, Hui
Wang, Wei
Zeng, Zhaoyang
Xiong, Wei
Li, Xiaoling
Li, Guiyuan
Zhou, Ming
author_facet Zhao, Ran
Liu, Yukun
Wu, Chunchun
Li, Mengna
Wei, Yanmei
Niu, Weihong
Yang, Jing
Fan, Songqing
Xie, Yong
Li, Hui
Wang, Wei
Zeng, Zhaoyang
Xiong, Wei
Li, Xiaoling
Li, Guiyuan
Zhou, Ming
author_sort Zhao, Ran
collection PubMed
description BRD7 functions as a crucial tumor suppressor in numerous malignancies. However, the effects of BRD7 on colorectal cancer (CRC) progression are still unknown. Here, based on the BRD7 knockout (BRD7(–/–)) and BRD7(flox/flox) (BRD7(+/+)) mouse models constructed in our previous work, we established an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse model. BRD7(+/+) mice were found to be highly susceptible to AOM/DSS-induced colitis-associated CRC, and BRD7 significantly promoted cell proliferation and cell cycle G1/S transition but showed no significant effect on cell apoptosis. Furthermore, BRD7 interacted with c-Myc and stabilized c-Myc by inhibiting its ubiquitin–proteasome-dependent degradation. Moreover, restoring the expression of c-Myc in BRD7-silenced CRC cells restored cell proliferation, cell cycle progression, and tumor growth in vitro and in vivo. In addition, BRD7 and c-Myc were both significantly upregulated in CRC patients, and high expression of these proteins was associated with clinical stage and poor prognosis in CRC patients. Collectively, BRD7 functions as an oncogene and promotes CRC progression by regulating the ubiquitin–proteasome-dependent stabilization of c-Myc protein. Targeting the BRD7/c-Myc axis could be a potential therapeutic strategy for CRC.
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spelling pubmed-81814132021-06-08 BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer Zhao, Ran Liu, Yukun Wu, Chunchun Li, Mengna Wei, Yanmei Niu, Weihong Yang, Jing Fan, Songqing Xie, Yong Li, Hui Wang, Wei Zeng, Zhaoyang Xiong, Wei Li, Xiaoling Li, Guiyuan Zhou, Ming Front Cell Dev Biol Cell and Developmental Biology BRD7 functions as a crucial tumor suppressor in numerous malignancies. However, the effects of BRD7 on colorectal cancer (CRC) progression are still unknown. Here, based on the BRD7 knockout (BRD7(–/–)) and BRD7(flox/flox) (BRD7(+/+)) mouse models constructed in our previous work, we established an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse model. BRD7(+/+) mice were found to be highly susceptible to AOM/DSS-induced colitis-associated CRC, and BRD7 significantly promoted cell proliferation and cell cycle G1/S transition but showed no significant effect on cell apoptosis. Furthermore, BRD7 interacted with c-Myc and stabilized c-Myc by inhibiting its ubiquitin–proteasome-dependent degradation. Moreover, restoring the expression of c-Myc in BRD7-silenced CRC cells restored cell proliferation, cell cycle progression, and tumor growth in vitro and in vivo. In addition, BRD7 and c-Myc were both significantly upregulated in CRC patients, and high expression of these proteins was associated with clinical stage and poor prognosis in CRC patients. Collectively, BRD7 functions as an oncogene and promotes CRC progression by regulating the ubiquitin–proteasome-dependent stabilization of c-Myc protein. Targeting the BRD7/c-Myc axis could be a potential therapeutic strategy for CRC. Frontiers Media S.A. 2021-05-24 /pmc/articles/PMC8181413/ /pubmed/34109174 http://dx.doi.org/10.3389/fcell.2021.659392 Text en Copyright © 2021 Zhao, Liu, Wu, Li, Wei, Niu, Yang, Fan, Xie, Li, Wang, Zeng, Xiong, Li, Li and Zhou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zhao, Ran
Liu, Yukun
Wu, Chunchun
Li, Mengna
Wei, Yanmei
Niu, Weihong
Yang, Jing
Fan, Songqing
Xie, Yong
Li, Hui
Wang, Wei
Zeng, Zhaoyang
Xiong, Wei
Li, Xiaoling
Li, Guiyuan
Zhou, Ming
BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer
title BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer
title_full BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer
title_fullStr BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer
title_full_unstemmed BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer
title_short BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer
title_sort brd7 promotes cell proliferation and tumor growth through stabilization of c-myc in colorectal cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181413/
https://www.ncbi.nlm.nih.gov/pubmed/34109174
http://dx.doi.org/10.3389/fcell.2021.659392
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