Decrement of miR-199a-5p contributes to the tumorigenesis of bladder urothelial carcinoma by regulating MLK3/NF-κB pathway.

Aberrant miRNA expression is implicated in tumorigenesis. However, the role of miRNAs in bladder urothelial carcinoma still remains largely unknown. In this study, miR-199a-5p was validated to be significantly down-regulated in bladder urothelial carcinoma. In addition, restoring expression of miR-199a-5p inhibited the tumorigenesis of bladder urothelial carcinoma in vitro and in vivo by inducing the apoptosis and suppressing the proliferation of bladder cancerous cells. Further investigation reported that MLK3 was a direct target of miR-199a-5p. Moreover, the expression level of miR-199a-5p was conversely correlated with MLK3 in bladder cancerous cells. In addition, reintroduction of MLK3 was identified to promote the proliferation and inhibit the apoptotic rate of cells, which have been altered by miR-199a-5p through activating the NF-kappa B pathway. All together, decrement of miR-199a-5p contributes to the tumorigenesis of bladder cancer by directly regulating MLK3/NF-kappa B pathway and miR-199a-5p might be developed as a therapeutic target for treatment of the bladder urothelial carcinoma.