Frontiers in Cell and Developmental Biology | |
BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer | |
Ran Zhao2  Yukun Liu2  Wei Wang2  Songqing Fan3  Yong Xie3  Hui Li3  Ming Zhou4  Zhaoyang Zeng6  Jing Yang6  Yanmei Wei6  Mengna Li6  Weihong Niu6  Wei Xiong6  Guiyuan Li6  Chunchun Wu6  Xiaoling Li6  | |
[1] Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, China;Department of Pathology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, China;Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, China;Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China;NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China;The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China; | |
关键词: BRD7; oncogene; c-Myc; deubiquitination; colorectal cancer; | |
DOI : 10.3389/fcell.2021.659392 | |
来源: DOAJ |
【 摘 要 】
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 BRD7flox/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.
【 授权许可】
Unknown