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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 of  PUF60  was significantly higher in tumor tissues, while high  PUF60  expression was associated with malignant phenotypes of bladder cancer and shorter survival time. Moreover, we identified aurora kinase A ( AURKA ) as a new downstream target of  PUF60  in bladder cancer cells.  PUF60  knockdown significantly inhibited cell viability and colony formation capacity in bladder cancer cells, whereas  AURKA  overexpression reversed this inhibition effect. Overexpression of  PUF60  significantly promoted cell viability and colony formation in bladder cancer cells, while treatment with  AURKA  specific inhibitor reversed this promotive effect. Mechanistically,  PUF60  specifically bound to the  AURKA  promoter, thereby activating its transcription and expression. Furthermore, we showed that there was a significant positive correlation between  PUF60  and  AURKA  expression in bladder cancer tissues, and  PUF60  and  AURKA  expression contributed to tumor progression and malignant phenotypes in the patients with bladder cancer. Collectively, these results indicate that the  PUF60/AURKA  axis 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.

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