Abstract

BRD7 functions as a crucial tumor suppressor in numerous malignancies including nasopharyngeal carcinoma (NPC). However, its function and exact mechanisms involved in tumor progression are not well understood. Here, we found that the B7BS was a potential enhancer region of BIRC2, and BRD7 negatively regulated the transcriptional activity and expression of BIRC2 by targeting the activation of the BIRC2 enhancer. Moreover, BIRC2 promoted cell proliferation, migration, invasion as well as xenograft tumor growth and metastasis in vivo, thus functioning as an oncogene in NPC. Furthermore, the recovery of BIRC2 expression could rescue the inhibitory effect of BRD7 on cell proliferation, migration, invasion and xenograft tumor growth and metastasis. In addition, BIRC2 was highly-expressed in NPC tissues, and positively correlated with the TNM stage and negatively correlated with the expression of BRD7. Therefore, these results suggest that BRD7 suppresses tumor growth and metastasis thus functioning as a tumor suppressor at least partially by negatively regulating the enhancer activity and expression of BIRC2, and targeting the BRD7/BIRC2 regulation axis might be a potential strategy for the diagnosis and treatment of NPC.

Details

Title
BRD7 inhibits enhancer activity and expression of BIRC2 to suppress tumor growth and metastasis in nasopharyngeal carcinoma
Author
Li, Mengna 1 ; Wei, Yanmei 2 ; Liu, Yukun 3 ; Wei, Jianxia 1 ; Zhou, Xiangting 4 ; Duan, Yumei 5 ; Chen, Shipeng 1 ; Xue, Changning 1 ; Zhan, Yuting 6 ; Zheng, Lemei 1 ; Deng, Hongyu 7 ; Tang, Faqing 7   VIAFID ORCID Logo  ; Fan, Songqing 6   VIAFID ORCID Logo  ; Xiong, Wei 1   VIAFID ORCID Logo  ; Li, Guiyuan 1 ; Tan, Ming 8 ; Zhou, Ming 1   VIAFID ORCID Logo 

1  Central South University, NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, Cancer Research Institute and School of Basic Medical Sciences, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
2  Central South University, Cancer Research Institute and School of Basic Medical Sciences, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
3  Central South University, NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, Cancer Research Institute and School of Basic Medical Sciences, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Jining Medical University, Department of Pathology, Affiliated Hospital of Jining Medical University, Jining, China (GRID:grid.449428.7) (ISNI:0000 0004 1797 7280) 
4  The first clinical college of Changsha Medical University, Changsha, China (GRID:grid.464229.f) (ISNI:0000 0004 1765 8757) 
5  Central South University, NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, Cancer Research Institute and School of Basic Medical Sciences, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
6  Central South University, Department of Pathology, the Second Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
7  Central South University, NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
8  China Medical University, Graduate Institute of Biomedical Sciences and Research Center for Cancer Biology, Taichung, Taiwan (GRID:grid.254145.3) (ISNI:0000 0001 0083 6092) 
Pages
121
Publication year
2023
Publication date
Feb 2023
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-023-05632-3
ProQuest document ID
2776289179
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.