OBJECTIVES: Bladder 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 METHODS: Northern 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 p27(kip1) 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. RESULTS: Human 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. CONCLUSIONS: MiRNA-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.
OBJECTIVES:Bladder 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 METHODS: Northern 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 p27(kip1) 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. RESULTS:HumanmiRNA-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. CONCLUSIONS:MiRNA-221 silencing rendered humanbladder cancer T24 cells to undergo apoptosis induced by TRAIL. Our findings suggest a potential role of suppressing miRNA-221 in humanbladder cancer therapy.
Authors: Elizabeth A Guancial; Joaquim Bellmunt; Shuyuan Yeh; Jonathan E Rosenberg; David M Berman Journal: Urol Oncol Date: 2013-08-02 Impact factor: 3.498
Authors: Mark T W Teo; Debora Landi; Claire F Taylor; Faye Elliott; Laurence Vaslin; David G Cox; Janet Hall; Stefano Landi; D Timothy Bishop; Anne E Kiltie Journal: Carcinogenesis Date: 2011-12-12 Impact factor: 4.944