Loss of Fezf2 promotes malignant progression of bladder cancer by regulating the NF-κB signaling pathway.

Forebrain embryonic zinc finger 2 (Fezf2) is an evolutionarily conserved zinc finger transcription repressor. It has been reported to be a tumor suppressor; however, neither the role that Fezf2 plays in bladder cancer nor the mechanisms involved have been investigated. In this study, we showed that Fezf2 expression is downregulated in bladder cancer tissues and cell lines compared to adjacent non-tumor tissues and normal urothelial cells. We also retrospectively analyzed the association between Fezf2 and various clinicopathologic characteristics in 196 bladder cancer patients, and showed that low expression of Fezf2 is correlated with larger tumor size, advanced tumor stage, and poor clinical prognosis. Moreover, we found that overexpression of Fezf2 significantly inhibited the proliferation, growth, migration, and invasion of bladder cancer cells, and attenuated angiogenesis, while knockdown of Fezf2 had the opposite effect. Fezf2 suppressed bladder cancer aggressiveness by activating the NF-κB signaling pathway. These findings suggest that Fezf2 holds promise as a prognostic biomarker, and provide a putative mechanism for bladder cancer progression.