MicroRNA-23b Functions as a Tumor Suppressor by Regulating Zeb1 in Bladder Cancer

University of Central Florida, United States of America
PLoS ONE (Impact Factor: 3.23). 07/2013; 8(7):e67686. DOI: 10.1371/journal.pone.0067686
Source: PubMed


MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation. In this study we show that miRNA-23b (miR-23b) acts as a tumor suppressor in bladder cancer. Quantitative real-time PCR analysis showed that miR-23b is significantly down-regulated in bladder cancer cell lines and tumor tissues compared to non-malignant cells and normal tissue samples. We also demonstrate that miR-23b expression has a potential to be diagnostic and prognostic biomarker in bladder cancer. High miR-23b expression is positively correlated with higher overall survival of bladder cancer patients as revealed by Kaplan-Meier analysis. ROC analysis showed that miR-23b expression can distinguish between normal and bladder cancer tissues. Further we elucidated the biological significance of miR-23b in bladder cancer. Over-expression of miR-23b in bladder cancer cells inhibited cell proliferation and impaired colony formation. Fluorescence activated cell sorting (FACS) analysis revealed that re-expression of miR-23b in bladder cancer cells induced G0/G1 cell cycle arrest and apoptosis while inhibiting cell migration and invasion. Luciferase reporter assays demonstrated that Zeb1, a crucial regulator of epithelial-to-mesenchymal transition (EMT), is a direct target of miR-23b in bladder cancer. These results show that loss of miR-23b confers a proliferative advantage and promotes bladder cancer cell migration and invasion. Furthermore, re-expression of miR-23b may be a beneficial therapeutic strategy for the treatment of human bladder cancer.

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    • "In which, many evidence pointed to the glycogen synthase kinase 3β- (GSK3β-) ZEB1 cascade which was triggered through phosphatidylinositol 3-kinase (PI3 K)/Akt pathways [49–51]. Further, noncoding RNA including microRNA-23b and long noncoding RNA MALAT-1 has also been suggested to be the transcriptional regulator of ZEB1 and ZEB2 in bladder cancers [52, 53]. "
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