HnRNP-F Regulates EMT in Bladder Cancer by Mediating the Stabilization of Snail1 MRNA by Binding to Its 3' UTR

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2019 Jun 22

PMID 31221586

Citations 31

Authors

Fei Li

Hongfan Zhao

Mingqiang Su

WeiWei Xie

Yunze Fang

Yuejun Du

Zhe Yu

Lina Hou

Wanlong Tan

Affiliations

Soon will be listed here.

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.

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