Disruption of serine/threonine protein phosphatase 5 inhibits tumorigenesis of urinary bladder cancer cells.

Serine/threonine protein phosphatase 5 (PPP5C) is a member of the protein serine/threonine phosphatase family and has been shown to participate in multiple signaling cascades and tumor progression. We found that PPP5C was highly expressed in bladder cancer tissues compared to normal urothelial tissues, and positively correlated to tumor stages through ONCOMINE microarray data mining. Knockdown of PPP5C via a lentivirus-mediated short hairpin RNA (shRNA) markedly inhibited cell proliferation and colony formation. Flow cytometric analysis showed that PPP5C-deficient T24 and BT5637 bladder cancer cells were arrested in G0/G1 phase and induced apoptosis. In addition, tumor growth was inhibited in vivo in a xenograft nude mouse model. Further studies indicated that knockdown of PPP5C downregulated c-myc and CDK4, whereas upregulated p27, BAD and Beclin1. These results suggest that PPP5C is associated with bladder cancer (BCa) and plays an oncogenic role in the development and progression of bladder cancer.