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Published on: June 17, 2014
Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/β-catenin feedback loop
Yan-Ping Zhang1,2, Kai-Long Liu2, Ya-Xuan Wang2
1Department of Obstetrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
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.
Insights
RNA-binding motif protein 5 (RBM5) is down-regulated in bladder cancer, inhibiting apoptosis. This activates a feedback loop involving miR-432-5p and β-catenin, promoting bladder cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- RNA-binding motif protein 5 (RBM5) is a known tumor suppressor in various cancers.
- The function of RBM5 in bladder urothelial carcinoma (BUC) has not been previously established.
Purpose of the Study:
- To investigate the role of RBM5 in bladder urothelial carcinoma.
- To elucidate the molecular mechanisms underlying RBM5's function in BUC.
Main Methods:
- Quantitative analysis of RBM5 expression in BUC tissues.
- Investigation of the regulatory relationship between RBM5, miR-432-5p, and β-catenin.
- Assessment of the impact of this feedback loop on bladder cancer cell apoptosis.
Main Results:
- RBM5 expression is significantly decreased in BUC tissues compared to adjacent non-tumor tissues.
- Down-regulation of RBM5 leads to increased β-catenin activity, up-regulating miR-432-5p.
- Up-regulated miR-432-5p directly targets and reduces RBM5 expression, forming a negative feedback loop.
Conclusions:
- A feedback loop involving RBM5, miR-432-5p, and β-catenin is identified in bladder cancer.
- This regulatory loop contributes to the inhibition of apoptosis and progression of bladder cancer cells.
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