MicroRNA-106a suppresses proliferation, migration, and invasion of bladder cancer cells by modulating MAPK signaling, cell cycle regulators, and Ets-1-mediated MMP-2 expression

Despite the clinical significance of tumorigenesis, little is known about the cellular signaling networks of microRNAs (miRs). Here we report a new finding that mir-106a regulates the proliferation, migration, and invasion of bladder cancer cells. Basal expression levels of mir-106a were significantly lower in bladder cancer cells than in normal urothelial cells. Overexpression of mir-106a suppressed the proliferation of bladder cancer cell line EJ. Transient transfection of mir-106a into EJ cells led to downregulation of ERK phosphorylation and upregulation of p38 and JNK phosphorylation over their levels in the control. Flow cytometry analysis revealed that mir-106a-transfected cells accumulated in the G1-phase of the cell cycle, and cyclin D1 and CDK6 were significantly down regulated. This G1-phase cell cycle arrest was due in part to the upregulation of p21(CIP1/WAF1). In addition, mir-106a overexpression blocked the wound-healing migration and invasion of EJ cells. Furthermore, mir-106a transfection resulted in decreased expression of MMP-2 and diminished binding activity of transcription factor Ets-1 in EJ cells. Collectively, we report the novel mir-106a-mediated molecular signaling networks that regulate the proliferation, migration, and invasion of bladder cancer cells, suggesting that mir-106a may be a therapeutic target for treating advanced bladder tumors.