circNR3C1 Suppresses Bladder Cancer Progression through Acting as an Endogenous Blocker of BRD4/C-myc Complex

Fei Xie; Xingyuan Xiao; Dan Tao; Chao Huang; Liang Wang; Feng Liu; Hui Zhang; Haitao Niu; Guosong Jiang

doi:10.1016/j.omtn.2020.09.016

circNR3C1 Suppresses Bladder Cancer Progression through Acting as an Endogenous Blocker of BRD4/C-myc Complex

Mol Ther Nucleic Acids. 2020 Sep 16:22:510-519. doi: 10.1016/j.omtn.2020.09.016. eCollection 2020 Dec 4.

Authors

Fei Xie^{1

2}, Xingyuan Xiao¹, Dan Tao³, Chao Huang¹, Liang Wang¹, Feng Liu¹, Hui Zhang¹, Haitao Niu², Guosong Jiang¹

Affiliations

¹ Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
² Department of Urology, Affiliated Hospital of Qingdao University, Qingdao 266013, China.
³ Department of Oncology, The Fifth Hospital of Wuhan, Wuhan 430050, China.

Abstract

Bromodomain-containing protein 4 (BRD4), the core component of transcriptional regulatory elements, plays a significant role in tumorigenesis and aggressiveness. However, the mechanisms regulating the functions of BRD4 in bladder cancer (BC) still remain elusive. Herein, we identify one exonic circular RNA (circRNA) generated from NR3C1 gene (circNR3C1) as a regulator of BRD4/C-myc complex. Our previous study indicated that BRD4 and C-myc promoter region form a complex, allowing C-myc to function as a transcription factor for BC progression. In the present study, mechanism studies reveal that circNR3C1 could interact with BRD4 protein, dissociating the formation of BRD4/C-myc complex. In vivo, ectopic expression of C-myc partly reverses the tumorigenesis of xenografts circNR3C1-induced in nude mice. Conclusively, these results demonstrate that circNR3C1 inhibits BC progression through acting as endogenous blocker of BRD4/C-myc complex.

Keywords: BRD4; bladder cancer; circNR3C1; endogenous blocker.