A positive feedforward circuit shaped by DLGAP5 and E2F1 triggers bladder cancer progression

Bladder cancer (BLCA) is a highly prevalent malignancy on a global scale, characterized by significant tumor heterogeneity. The investigation of molecular mechanisms that can be leveraged for the management of aggressive BLCA represents a particularly pertinent objective.DLGAP5 is mitosis-related protein widely existed in eukaryotic cells. The molecular mechanism of DLGAP5 in bladder cancer is still not clear, despite its role in tumorigenesis. Bladder cancer tissues exhibit a noteworthy increase in DLGAP5 expression, compared to normal bladder tissues. Furthermore, the expression of DLGAP5 shows a positive correlation with the clinical stage of the tumor and a negative impact on the prognosis. Cell proliferation and migration are significantly impacted by alterations in DLGAP5 expression, as demonstrated by in vitro and in vivo experiments. Further investigation reveals that DLGAP5 regulated E2F1 protein stability via USP11 deubiquitinase activity, and DLGAP5 is a direct target of E2F1. DLGAP5-E2F1 forms a positive feedback loop and influences the efficacy of BLCA progression. Collectively, DLGAP5 could potentially serve as a new therapeutic target for the treatment of bladder cancer. Overall design: In our exploration of the role played by the DLGAP5 gene in bladder cancer development, we conducted gene expression profiling analysis utilizing RNA-seq data acquired from T24 cells.