HnRNP-F regulates EMT in bladder cancer by mediating the stabilization of Snail1 mRNA by binding to its 3′ UTR

作者：Fei Li, Hongfan Zhao, Mingqiang Su, Weiwei Xie, Yunze Fang, Yuejun Du, Zhe Yu, Lina Hou, Wanlong Tan · 发表于：EBioMedicine · 年份：2019 · DOI：10.1016/j.ebiom.2019.06.017 · 被引用次数：58 · 研究领域：RNA Research and Splicing、Cancer Cells and Metastasis、RNA modifications and cancer

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 m...