MicroRNA-892b influences proliferation, migration and invasion of bladder cancer cells by mediating the p19ARF/cyclin D1/CDK6 and Sp-1/MMP-9 pathways

Abstract

Cancers often utilize microRNAs to suppress tumor suppressor genes, thus facilitating their potential for growth and invasion. In the present study, we report the novel findings that MIR-892b inhibits proliferation, migration and invasion of bladder cancer cells. The basal expression level of MIR-892b was significantly lower in 3 different bladder cancer cell lines than in normal human urothelial cells. Transfection of MIR-892b mimics to bladder cancer cells resulted in dose-dependent growth arrest. Flow cytometric analysis of the cell cycle showed that MIR-892b-transfected bladder cancer cells were subject to arrest in the G1 phase, which was due to the downregulation of cyclin D1 and CDK6 followed by upregulation of p19ARF. In addition, overexpression of MIR-892b impeded the migration and invasion of EJ cells. Expression of MMP-9 in EJ cells was blocked by transfection of MIR-892b; the effect was regulated, at least in part, by activation of the Sp-1 transcription factor. Overall, we verified that MIR-892b regulates the p19ARF/cyclin D1/CDK6 and Sp-1/MMP-9 signaling networks in bladder cancer cells and may provide a treatment option for advanced-stage bladder cancers.