The Anti-tumor Role And Mechanism Of MiR-381-3p In Bladder Cancer

Emerging evidence has shown that bladder cancer becomes more and more common in the world and rank the second in tumors of urinary system;New therapies came out every year to control it but its progress and metastasis still threaten the patients.MicroRNA are small non-coding RNAs that showed potential to be target gene regulators in the therapy of tumors recently,and many miRNAs in the DLK-DI03 imprinted domain were proved to be involved in bladder cancer proliferation and migration.In this study,we mainly investigated the functions and regulatory mechanisms of miR-381-3p in bladder cancer.We found that the MEG3 differentially methylated region(MEG3-DMR)downregulated the expression of miR-381-3p in bladder cancer.Overexpression of miR-381-3p suppressed the proliferation by inducing the cell cycle G1 phase arrest,and the EMT progress by targting MET and CCNA2.We also use bioinformatic analysis and Dual-Luciferase Reporter Assay to identify that CDK6,CCNA2,MET are all direct targets of miR-381-3p.Futhermore,we found that downregulation of CCNA2 expression not only blocked the cell cycle,but also suppressed the EMT progression via ROCK/AKT/β-catenin/SNAIL pathway,and SNAIL is the last confocal target to induce EMT progression.We also proved that overexpression of miR-381-3p inhibits the proliferation and metastasis in vivo.In conclusion,we proved that overexpression of miR-381-3p suppressed the proliferation and EMT progression by regulating its direct targets CCNA2,CDK6 and MET in bladder cancer,which may contribute to the development of new therapies against bladder cancer in the future.