Journal
EBIOMEDICINE
Volume 45, Issue -, Pages 208-219Publisher
ELSEVIER
DOI: 10.1016/j.ebiom.2019.06.017
Keywords
Bladder cancer; Heterogeneous nuclear ribonucleoprotein F; Snail1; Stabilization; Epithelial-mesenchymal transition
Funding
- Natural Science Foundation Committee of China [NSFC 81802941]
- Natural Science Foundation of Guangdong Province of China [2018A0303130287]
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Background: Heterogeneous nuclear ribonucleoprotein F (hnRNP-F) has been implicated inmultiple cancers, suggesting its role in tumourigenesis, but the potential oncogenic role and mechanismof 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. (C) 2019 Published by Elsevier B.V.
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