AB265. Association between MDM2 SNP309T>G polymorphism and the risk of bladder cancer: new data in Chinese population and an update meta-analysis

Background: To investigate the role of miR-186 in the carcinogenesis and metastasis of human urothelial bladder cancer and its potential target protein. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect miR-186 expression in human urothelial bladder cancer tissues and cell lines. Then, Bioinformatics analysis, combined with luciferase reporter assay demonstrated the miR-186’s target gene and protein. Finally, the roles of miR-186 in regulation of tumor proliferation and invasion were further investigated by MTT assay and transwell assay. Results: MiR-186 was down-regulated in human urothelial bladder cancer tissues and cell lines. Luciferase reporter assay showed that miR-186 targets HMGN5 3'-untranslated region (UTR) directly and suppresses HMGN5 expression in human urothelial bladder cancer cells. HMGN5 siRNAand miR-186-mediated HMGN5 knock-down experiments revealed that miR-186 suppresses cell proliferation and invasion through suppression of HMGN5 expression. Expression analysis of a set of epithelial-mesenchymal transition (EMT) markers showed that HMGN5 involves miR-186 suppressed EMT which reducing the expression of mesenchymal markers (vimentin and N-cadherin) and inducing the expression of epithelial marker (E-cadherin). Conclusions: MiR-186 is the upstream regulator of HMGN5. MiR-186-suppressed HMGN5 is a potential novel therapeutic approach for human urothelial bladder cancer.