Nucleoporin 93 Regulates Cancer Cell Growth and Stemness in Bladder Cancer via Wnt/β-Catenin Signaling

Bladder Cancer (BLCA) is a prevalent Cancer type with an unmet need for new therapeutic strategies. Nucleoporin 93 (Nup93) is implicated in the pathophysiology of several cancers, but its relationship with bladder Cancer remains unclear. Nup93 expression was analyzed in TCGA datasets and 88 BLCA patient samples. Survival analysis and COX regression models evaluated the association between Nup93 levels and patient prognosis. BLCA cells were used to investigate the effects of Nup93 overexpression or knockdown on cell growth, invasion, stemness (sphere formation and ALDH2 + Cancer stem cell marker), and Wnt/β-catenin signaling in vitro. The Wnt activator BML-284 was used to confirm the involvement of Wnt/β-catenin signaling pathway. A xenograft mouse model validated the in vitro findings. Nup93 was highly expressed in BLCA tissues and cell lines, and high Nup93 expression correlated with poor prognosis in BLCA patients. Nup93 silencing inhibited BLCA cell proliferation, Wnt/β-catenin activation, and Cancer cell stemness. Conversely, Nup93 overexpression promoted these effects. BML-284 partially rescued the reduction in cell growth and stemness markers caused by Nup93 knockdown. Nup93 knockdown also suppressed the tumor formation of BLCA cells in vivo. Nup93 regulates BLCA cell growth and stemness via the Wnt/β-catenin pathway, suggesting its potential as a prognostic marker and therapeutic target in BLCA.

Bladder cancer; Cancer stem cell; Cell proliferation; Nucleoporin 93; Wnt/β-catenin pathway.