Department of Urology, VA Medical Center and UCSF, San Francisco, California, USA.
PLoS One. 2013 Jul 2;8(7):e67686. doi: 10.1371/journal.pone.0067686. Print 2013.
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.
微小 RNA（miRNAs）是一种小的非编码 RNA，可以通过靶向抑制转录和翻译来调节基因表达。在本研究中，我们表明 miRNA-23b（miR-23b）在膀胱癌中作为一种肿瘤抑制因子发挥作用。定量实时 PCR 分析显示，与非恶性细胞和正常组织样本相比，miR-23b 在膀胱癌细胞系和肿瘤组织中显著下调。我们还证明，miR-23b 的表达有可能成为膀胱癌的诊断和预后生物标志物。Kaplan-Meier 分析显示，miR-23b 高表达与膀胱癌患者的总生存率呈正相关。ROC 分析显示，miR-23b 的表达可以区分正常组织和膀胱癌组织。此外，我们阐明了 miR-23b 在膀胱癌中的生物学意义。在膀胱癌细胞中过表达 miR-23b 抑制细胞增殖并损害集落形成。荧光激活细胞分选（FACS）分析显示，miR-23b 在膀胱癌细胞中的重新表达诱导 G0/G1 细胞周期停滞和凋亡，同时抑制细胞迁移和侵袭。荧光素酶报告基因检测表明，Zeb1 是上皮间质转化（EMT）的关键调节因子，是膀胱癌中 miR-23b 的直接靶标。这些结果表明，miR-23b 的缺失赋予了增殖优势，并促进了膀胱癌细胞的迁移和侵袭。此外，miR-23b 的重新表达可能是治疗人类膀胱癌的有益治疗策略。
