TAZ Regulate Bladder Cancer Cell Proliferation And Apoptosis Via P38 Activity

Background and aims: Bladder cancer is the most common urology tumor which leads to cancer-related death in the world.Surgery,radiation therapy and chemotherapy are current major therapies but survival rates are still disappointment.One of the major reasons is the molecular mechanism of bladder cancer progression remains elusive.Among the signaling,Hippo pathway and p38 MAPK pathway are two very important ones.The core of Hippo pathway consists of a multiple components kinase cascade which induces phosphorylation and suppression of downstream transcriptional activators,YAP and TAZ.Deregulation of YAP,TAZ or other Hippo pathway components will cause diseases including many types of cancer.P38 MAPK signaling is another highly conserved pathway which governs cell growth and death.In this research,we bought shRNA vectors containing sequence targeting TAZ coding region to study the function of TAZ in bladder cancer cells.In addition,we explored functional interaction between Hippo signaling and p38 signaling.Methods and results:First,We performed RT-qPCR to confirm TAZ sh RNA efficiency.Second,we used the bladder cancer cell lines T24 and 5637 to perform the cell proliferation assay.The CCK-8 and Ed U cell proliferation assay showed that knockdown of TAZ inhibits cell proliferation.To examine cell apoptosis,we analyzed expression of caspase3 and cleaved-caspase3 by western blot and the results showed that knockdown of TAZ induces apoptosis.Moreover,western blot assay also suggested that TAZ may regulate p38 protein stability.Finally,we used a p38 inhibitor PH-797804 to block p38 activity in TAZ knockdown condition in western blot assay and cell proliferation assay.The results showed that p38 activity mediates regulation of proliferation and apoptosis by TAZ.Conclusions: TAZ plays an oncogenic role in the development of bladder cancer,and it may become a new tumor marker and therapeutic target for early diagnosis and advanced treatment.The TAZ sh RNA may open up a new method for bladder cancer in vitro study.