RBM11 drives malignant progression of bladder cancer by regulating GNPDA1-PKM2 axis.

This study investigated the biological functions and molecular mechanisms of RNA-binding motif protein 11 (RBM11) in bladder cancer (BCa) progression. Integrated bioinformatics analysis of the TCGA database and validation in clinical tissues revealed that RBM11 is significantly upregulated in BCa and positively correlated with advanced tumor stage, poor prognosis, and epithelial-mesenchymal transition (EMT). RBM11 knockdown effectively suppressed migration, invasion, proliferation, and chemoresistance of BCa cells, whereas RBM11 overexpression produced opposite effects. Mechanistically, RBM11 promotes GNPDA1 expression by regulating alternative splicing of GNPDA. Furthermore, GNPDA1 directly interacts with PKM2 and inhibits its ubiquitin-proteasome-mediated degradation, thereby stabilizing PKM2 protein levels, enhancing glycolysis, and promoting malignant progression of BCa. Collectively, these findings indicate that RBM11 drives malignant progression of BCa through the GNPDA1-PKM2 axis, enhancing glucose metabolism reprogramming and EMT process, suggesting that RBM11 may be a potential therapeutic target for BCa.