CircBRD7 inhibits tumor growth and metastasis in nasopharyngeal carcinoma via forming a positive feedback regulation loop with its host gene

Abstract Background: BRD7 was identified as a tumor suppressor in nasopharyngeal carcinoma (NPC). Circular RNA (CircRNAs) are involved in the occurrence and development of NPC as oncogenes or tumor suppressors. However, the function and mechanism of the circRNAs derived from BRD7 in NPC are not well understood. Methods: Bioinformatics analysis, agarose gel electrophoresis and Sanger sequencing were performed to screen and identify the circular RNA derived from BRD7. CCK-8, colony formation, wound healing and transwell assays were used to evaluate the cell proliferation, migration and invasion abilities of circBRD7. The ChIP-qPCR assay was performed to investigate the regulatory mechanism of circBRD7 on BRD7. Xenograft tumor and lung metastasis models were constructed to confirm the effect of circBRD7 on tumor growth and metastasis. Results: CircBRD7 was identified as a circular RNA derived from BRD7 that inhibited cell proliferation, migration, invasion of NPC cells as well as the xenograft tumor growth and metastasis in vivo. Mechanistically,circBRD7 promoted the transcription and expression of BRD7 by enhancing the enrichment of H3K27ac in the promoter region of its host gene, and BRD7 promoted the expression of circBRD7, thus circBRD7 formed positive feedback loop with BRD7 to inhibit NPC development and progression. Moreover, restoration of BRD7 expression rescued the inhibitory effect of circBRD7 on the proliferation, migration and invasion of NPC cell and xenograft tumor growth and metastasis. In addition, circBRD7 was expressed at low levels in NPC tissues, which was positively correlated with BRD7 expression and negatively correlated with the clinical stage of NPC patients. The combination of circBRD7 and BRD7 could be used as an important molecular marker for the evaluation of NPC progression. Conclusions: Taken together, circBRD7 inhibits the tumor growth and metastasis of NPC via forming positive feedback loop with its host gene, and targeting the circBRD7/BRD7 axis is a promising strategy for the clinical diagnosis and treatment of NPC.