POC1A promotes the proliferation, metastasis and stemness of bladder cancer by stabilizing BMI1 via USP7.

Advanced bladder cancer (BLCA), a malignancy with high recurrence, carries a dismal prognosis, demanding the identification of novel therapeutic targets. In this study, we aim to investigate a critical molecular mechanism driving BLCA progression. By integrating published sequencing datasets, we identified that POC1A is overexpressed in BLCA tissues, a factor positively correlated with advanced stage, high grade, disease progression, and inversely correlated with overall survival. In vitro and in vivo analyses indicate that POC1A knockdown inhibits BLCA cell proliferation, metastasis, and stemness. Mechanistically, POC1A functions as a scaffold protein, forming a complex with USP7 and BMI1. This enhances the USP7-BMI1 interaction, reduces BMI1 ubiquitination in a USP7-dependent manner, and consequently stabilizes the BMI1 protein. The functional significance of this pathway was confirmed as overexpression of either BMI1 or USP7 rescued the inhibitory phenotypes induced by POC1A knockdown. Furthermore, pharmacological targeting of BMI1 with Unesbulin suppressed BLCA growth in cell-line and patient-derived xenograft models, supporting the therapeutic tractability of the POC1A-BMI1 axis. Taken together, these findings reveal that POC1A facilitates the USP7-mediated deubiquitination and stabilization of BMI1, establishing the POC1A-USP7-BMI1 complex as a compelling therapeutic target in BLCA.