BRD7 inhibits enhancer activity and expression of BIRC2 to suppress tumor growth and metastasis in nasopharyngeal carcinoma

Abstract

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 is a potential enhancer region of BIRC2, and BRD7 negatively regulates the transcriptional activity and expression of BIRC2 by targeting the activation of the BIRC2 enhancer. Moreover, BIRC2 promotes 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 can rescue the inhibitory effect of BRD7 on cell proliferation, migration, invasion and xenograft tumor growth and metastasis. In addition, BIRC2 is high-expressed in NPC biopsy tissues, and is positively correlated with 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 via negatively regulating the enhancer activity and expression of BIRC2, and targeting the BRD7/BIRC2 regulation axis is a potential strategy for the diagnosis and treatment of nasopharyngeal carcinoma.