RNF26-mediated ubiquitination of TRIM21 promotes bladder cancer progression

RNF26 is an important E3 ubiquitin ligase that has been associated with poor prognosis in bladder cancer. However, the underlying mechanisms of RNF26 in bladder cancer tumorigenesis are not fully understood. In the present study, we found that RNF26 expression level was significantly upregulated in the bladder cancer tissues, and higher RNF26 expression is closely associated with poorer prognosis, lower immune cell infiltration, and more sensitive to immune checkpoint blockade drugs and chemotherapy drugs, including cisplatin, VEGFR-targeting drugs and MET-targeting drugs. RNF26 knockdown in UMUC3 and T24 cell lines inhibited cell growth, colony forma-tion and migratory capacity. Meanwhile, RNF26 overexpression had the opposite effects. Mechanistically, RNF26 exerts its oncogenic function by binding to TRIM21 and promoting its ubiquitination and subsequent degradation. Moreover, we revealed ZHX3 as a downstream target of RNF26/TRIM21 pathway in bladder cancer. Taken together, we identified a novel RNF26/TRIM21/ZHX3 axis that promotes bladder cancer progression. Thus, the RNF26/TRIM21/ZHX3 axis constitutes a potential efficacy predictive marker and may serve as a therapeutic target for the treatment of bladder cancer.