1. HnRNP-F regulates EMT in bladder cancer by mediating the stabilization of Snail1 mRNA by binding to its 3′ UTRResearch in context
- Author
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Fei Li, Hongfan Zhao, Mingqiang Su, Weiwei Xie, Yunze Fang, Yuejun Du, Zhe Yu, Lina Hou, and Wanlong Tan
- Subjects
Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Heterogeneous nuclear ribonucleoprotein F (hnRNP-F) has been implicated in multiple cancers, suggesting its role in tumourigenesis, but the potential oncogenic role and mechanism of hnRNP-F in bladder cancer (BC) remain incompletely understood. Methods: HnRNP-F was identified by proteomic methods. A correlation of hnRNP-F expression with prognosis was analysed in 103 BC patients. Then, we applied in vitro and in vivo methods to reveal the behaviours of hnRNP-F in BC tumourigenesis. Furthermore, the interaction between hnRNP-F and Snail1 mRNA was examined by RNA immunoprecipitation (RIP), and Snail1 mRNA stability was measured after treatment with actinomycin D. Finally, the binding domain between hnRNP-F and Snail1 mRNA was verified by constructing Snail1 mRNA truncations and mutants. Finding: HnRNP-F is significantly upregulated in BC tissue, and its increased expression is associated with a poor prognosis in BC patients. HnRNP-F is necessary for tumour growth, inducing epithelial-mesenchymal transition (EMT) and metastasis in BC. The changes in Snail1 expression were positively correlated with hnRNP-F at both the mRNA and protein levels when hnRNP-F was silenced or enhanced, suggesting that Snail1 is likely a downstream target of hnRNP-F that mediates its effects on enhancing invasion, metastasis and EMT in BC. The overexpression of hnRNP-F caused an increase in the stability of Snail1 mRNA. Our RNA chip analysis revealed that hnRNP-F could combine with Snail1 mRNA, and we further demonstrated that hnRNP-F could directly bind to the 3′ untranslated region (3′ UTR) of Snail1 mRNA to enhance its stability. Interpretation: Our findings suggest that hnRNP-F mediates the stabilization of Snail1 mRNA by binding to its 3′ UTR, subsequently regulating EMT. Keywords: Bladder cancer, Heterogeneous nuclear ribonucleoprotein F, Snail1, Stabilization, Epithelial-mesenchymal transition
- Published
- 2019
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