TAILIEUCHUNG - Báo cáo khoa học: microRNA-203 suppresses bladder cancer development by repressing bcl-w expression

It is increasingly clear that microRNAs (miRNAs) play an important role in many diseases, including tumorigenesis. However, the mechanisms by which miRNAs regulate bladder cancer development remain poorly under-stood. | BFEBS Journal microRNA-203 suppresses bladder cancer development by repressing bcl-w expression Juanjie Bo Guoliang Yang Kailing Huo Haifeng Jiang Lianhua Zhang Dongming Liu and Yiran Huang Department of Urology Renji Hospital Shanghai Jiaotong University China Keywords apoptosis bcl-w bladder cancer miR-203 proliferation Correspondence D. Liu Department of Urology Renji Hospital Schoolof Medicine Shanghai Jiaotong University No. 145 Shan Dong Middle Road Shanghai 200001 China Fax 86 21 6373 0455 Tel 86 21 6373 0455 E-mail dmliu@ Received 16 November 2010 revised 13 December 2010 accepted 22 December 2010 doi It is increasingly clear that microRNAs miRNAs play an important role in many diseases including tumorigenesis. However the mechanisms by which miRNAs regulate bladder cancer development remain poorly understood. Here we evaluated the expression of microRNA-203 miR-203 in bladder cancer tissues using real-time PCR and defined the target genes and biologically functional effect using luciferase reporter assay flow cytometry and western blot analysis. We first verified that the expression of miR-203 was decreased in bladder cancer tissues. Moreover ectopic expression of miR-203 promoted the apoptosis of human bladder cancer cell lines and inhibited cell proliferation whereas its depletion increased cell growth. We further verified that miR-203 directly targeted 3 -untranslated region of the bcl-w gene and decreased its expression in vitro and in vivo. Western blot analysis also showed that the expression level of miR-203 was negatively correlated with bcl-w level in tumor tissues. These data suggest an important role for miR-203 in the molecular etiology of bladder cancer and implicate the potential application of miR-203 in bladder cancer therapy. Introduction Human bladder cancer is the fourth most common malignancy in men and the tenth most common in women 1 . Molecular and pathological studies suggest that bladder

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