MicroRNA-221 silencing predisposed human bladder cancer cells to undergo apoptosis induced by TRAIL

ObjectivesBladder cancer is the most common type of urologic cancer in Chinese males. The 5-year survival rate of advanced bladder cancer is approximately 20%–40%. There is an obvious urgent need for novel and effective therapies against bladder cancer. MicroRNAs (miRNAs) are a recently discovered class of noncoding RNAs; suppressing miRNA-221 might prove beneficial in several cancers. To explore novel and effective therapies against bladder cancer, we explored the effects of miRNA-221 silencing on the survival of bladder cancer cells.Materials and methodsNorthern blot analysis was used to determine miRNA-221 expression levels in bladder cancer T24 cells, RT4 cells and human normal urothelial cells. miRNA-221 was silenced with antisense oligonucleotides in T24 cells and pro-apoptotic effect of necrosis factor related apoptosis-inducing ligand (TRAIL) on miRNA-221-silenced cells was assessed with flow cytometry. The p27kip1 protein expression in miRNA-221-silenced cells exposed to TRAIL was detected by Western blotting. The role of miRNA-221 silencing on T24 cell cycle phase distribution was investigated through flow cytometric analysis.ResultsHuman miRNA-221 was significantly up-regulated in bladder cancer T24 cells and RT4 cells compared to human normal urothelial cells. T24 cell was TRAIL-resistant cell line. MiRNA-221 silencing predisposed T24 cells to undergo apoptosis induced by TRAIL and resulted in an up-modulation of cyclin-dependent kinase inhibitor p27Kip1. MiRNA-221 suppression promoted the activation of caspase 3 induced by TRAIL in T24 cells.ConclusionsMiRNA-221 silencing rendered human bladder cancer T24 cells to undergo apoptosis induced by TRAIL. Our findings suggest a potential role of suppressing miRNA-221 in human bladder cancer therapy.