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下调 RBM5 通过引发 miR-432-5p/β-catenin 反馈环抑制膀胱癌细胞凋亡。

Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/β-catenin feedback loop.

机构信息

Department of Obstetrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

FASEB J. 2019 Oct;33(10):10973-10985. doi: 10.1096/fj.201900537R. Epub 2019 Jul 18.

Abstract

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.

摘要

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。

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