CircRNA-cZFR is upregulated in bladder cancer and promotes tumorigenesis via UBE2V1 regulation

Circular RNA (circRNA), which encompasses a large range of endogenous RNA, can control the expression of genes in cancer. However, the function of circRNA in tumor stem cells remains largely unknown. In this study, we obtained circRNA and mRNA microarray data from bladder cancer stem cells (BCSCs) and non-bladder cancer stem cells (NBCSCs) derived from 3 patients. We performed functional validation of putative mechanisms using established low expression of cZFR bladder cancer cell lines. We found that the circRNA cZFR is overexpressed in BCSCs. Downregulation of cZFR inhibited cell sphere formation, invasion, migration, and BC cell proliferation. By analyzing the co-expression network of expressed circRNAs and dysregulated mRNAs, we determined that UBE2V1 is a target gene regulated by cZFR. Mechanistically, cZFR shares miRNA response elements with UBE2V1. cZFR binds to miR-511 and prevents miR-511 from decreasing the level of UBE2V1, which was upregulated in BCSCs and correlated with poor prognosis. Finally, we found that the expression of cZFR in the urine exosomes of patients was increased compared to normal. Our results suggest that cZFR may have regulatory functions in BC. cZFR is expected to be a biomarker for prognostic evaluation and a therapeutic target in BC.