PUF60/AURKAAxis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer

Abnormal expression or mutation of RNA splicing proteins are widely observed in human cancers. Here, we identified poly(U) binding splicing factor 60 (PUF60) as one of the most differentially expressed genes out of 97 RNA splicing proteins between normal and bladder cancer tissues by bioinformatics analysis of TCGA bladder cancer expression data. The expression ofPUF60was significantly higher in tumor tissues, while highPUF60expression was associated with malignant phenotypes of bladder cancer and shorter survival time. Moreover, we identified aurora kinase A (AURKA) as a new downstream target ofPUF60in bladder cancer cells.PUF60knockdown significantly inhibited cell viability and colony formation capacity in bladder cancer cells, whereasAURKAoverexpression reversed this inhibition effect. Overexpression ofPUF60significantly promoted cell viability and colony formation in bladder cancer cells, while treatment withAURKAspecific inhibitor reversed this promotive effect. Mechanistically,PUF60specifically bound to theAURKApromoter, thereby activating its transcription and expression. Furthermore, we showed that there was a significant positive correlation betweenPUF60andAURKAexpression in bladder cancer tissues, andPUF60andAURKAexpression contributed to tumor progression and malignant phenotypes in the patients with bladder cancer. Collectively, these results indicate that thePUF60/AURKAaxis plays a key role in regulating tumorigenesis and progression of bladder cancer, and may be a potential prognostic biomarker and therapeutic target for bladder cancer patients.