Department of Obstetrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
FASEB J. 2019 Oct;33(10):10973-10985. doi: 10.1096/fj.201900537R. Epub 2019 Jul 18.
RNA-binding motif protein 5 (RBM5) acts as a tumor suppressor in various human cancers and presents with several important characteristics, such as the potentiation of apoptosis, inhibition of the cell cycle, and alternative splicing of Fas and caspase-2 precursor mRNA. However, its role in bladder urothelial carcinoma (BUC) remains unknown. In this study, we found that RBM5 expression was significantly down-regulated in BUC tissues when compared with the adjacent nontumor tissues. The down-regulation of RBM5 activates β-catenin, which binds to the T-cell factor/lymphocyte enhancer factor element of the miR-432-5p promoter and elevates the expression of miR-432-5p in bladder cancer cells. The up-regulated miR-432-5p directly targets 3'-UTR and depresses RBM5 expression. Thus, RBM5-miR-432-5p-β-catenin forms a feedback loop in regulating bladder cancer cell apoptosis. Our findings provide evidence that the regulatory feedback loop among RBM5, miR-432-5p, and Wnt-β-catenin is responsible for the progress of bladder cancer cells.-Zhang, Y.-P., Liu, K.-L., Wang, Y.-X., Yang, Z., Han, Z.-W., Lu, B.-S., Qi, J.-C., Yin, Y.-W., Teng, Z.-H., Chang, X.-L., Li, J.-D., Xin, H., Li, W. Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/β-catenin feedback loop.
RNA 结合基序蛋白 5(RBM5)在各种人类癌症中作为肿瘤抑制因子发挥作用,并具有多个重要特征,例如促进细胞凋亡、抑制细胞周期以及 Fas 和 caspase-2 前体 mRNA 的选择性剪接。然而,其在膀胱尿路上皮癌(BUC)中的作用尚不清楚。在本研究中,我们发现与相邻非肿瘤组织相比,RBM5 在 BUC 组织中的表达显著下调。RBM5 的下调激活了β-连环蛋白,β-连环蛋白结合 miR-432-5p 启动子的 T 细胞因子/淋巴细胞增强因子元件,并上调膀胱癌细胞中 miR-432-5p 的表达。上调的 miR-432-5p 直接靶向 3'-UTR 并抑制 RBM5 的表达。因此,RBM5-miR-432-5p-β-catenin 在调节膀胱癌细胞凋亡中形成一个反馈回路。我们的研究结果提供了证据表明,RBM5、miR-432-5p 和 Wnt-β-连环蛋白之间的调控反馈环是负责膀胱癌细胞进展的原因。