NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410078, China.
Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, 410078, China.
Cell Death Dis. 2023 Feb 14;14(2):121. doi: 10.1038/s41419-023-05632-3.
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.
BRD7 在包括鼻咽癌(NPC)在内的众多恶性肿瘤中作为一个重要的肿瘤抑制因子发挥作用。然而,其在肿瘤进展中发挥功能的具体机制尚不清楚。在这里,我们发现 B7BS 是 BIRC2 的一个潜在增强子区域,BRD7 通过靶向 BIRC2 增强子的激活,负调控 BIRC2 的转录活性和表达。此外,BIRC2 促进 NPC 细胞的增殖、迁移、侵袭以及体内异种移植肿瘤的生长和转移,从而发挥癌基因的作用。此外,恢复 BIRC2 的表达可以挽救 BRD7 对细胞增殖、迁移、侵袭和异种移植肿瘤生长和转移的抑制作用。另外,BIRC2 在 NPC 组织中高表达,并且与 TNM 分期呈正相关,与 BRD7 的表达呈负相关。因此,这些结果表明 BRD7 通过负调控 BIRC2 的增强子活性和表达来抑制肿瘤生长和转移,至少部分发挥肿瘤抑制因子的作用,靶向 BRD7/BIRC2 调控轴可能是 NPC 诊断和治疗的一种潜在策略。