MiR-708 promotes the development of bladder carcinoma via direct repression of Caspase-2

摘要

Purpose: Bladder cancer is one of the world's top ten malignant tumors. The crucial role of microRNA in carcinogenesis has been well emphasized. Considering miRNA expression was tumor stage-, tissue-, or even development-specific, more experimental evidences about the functions of miRNAs in bladder cancer should be discovered to advance applying of miRNA in the diagnosis or therapy of cancer. Methods: MiR-708 level in bladder carcinoma and adjacent noncancerous tissues was tested by real-time qPCR. Cell apoptosis was analyzed by using flow cytometry. The tumorigenicity of bladder carcinoma cells was evaluated in nude mice model. Luciferase reporter gene assays were performed to identify the interaction between miR-708 and 3′UTR of Caspase-2 mRNA. The protein level of Caspase-2 was determined by western blotting. Results: In this study, we reported that miR-708 was frequently dysregulated in human bladder carcinoma tissues compared to normal tissues. In addition, we found that silencing of miR-708 could promote the T24 and 5637 cells to apoptosis and inhibit the bladder tumor growth in vivo. Also, Caspase-2 was proved to be one of direct targets of miR-708 in T24 and 5637 cells. Further results showed that Caspase-2 was involved in the miR-708 regulated cell apoptosis. Conclusions: All together, these results suggest miR-708 may act as an oncogene and induce the carcinogenicity of bladder cancer by down-regulating Caspase-2 level.