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EZH2 contributes to 5-FU resistance in gastric cancer by epigenetically suppressing FBXO32 expression

Authors Wang C, Li X, Zhang J, Ge Z, Chen H, Hu J

Received 13 July 2018

Accepted for publication 27 August 2018

Published 5 November 2018 Volume 2018:11 Pages 7853—7864

DOI https://doi.org/10.2147/OTT.S180131

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Sanjeev Srivastava


Chenyu Wang,* Xingwang Li,* Junjie Zhang, Zheng Ge, Hejin Chen, Junhong Hu

Department of Anorectal, Huaihe Hospital of Henan University, Kaifeng, 475000, People’s Republic of China

*These authors contributed equally to this work

Background: Increasing evidence suggests the involvement of enhancer of zeste homologue 2 (EZH2) in chemoresistance of cancer treatment. Nevertheless, its function and molecular mechanisms in gastric cancer (GC) chemoresistance are still not well elucidated.
Materials and methods: In the present study, we investigated the functional role of EZH2 in 5-fluorouracil (5-FU) resistance of GC cells and discovered the underlying molecular mechanism.
Results: Results revealed that EZH2 was upregulated in 5-FU-resistant GC tissues and cell lines. High ZEH2 expression was correlated with poor prognosis of GC patients. EZH2 knockdown enhanced 5-FU sensitivity of AGS/5-FU and SGC-7901/5-FU cells. Moreover, EZH2 could epigenetically suppress FBXO32 expression. FBXO32 overexpression could mimic the functional role of downregulated EZH2 in 5-FU resistance. FBXO32 knockdown counteracted the inductive effect of EZH2 inhibition on 5-FU sensitivity of AGS/5-FU and SGC-7901/5-FU cells. Furthermore, EZH2 knockdown facilitated 5-FU sensitivity of 5-FU-resistant GC cells in vivo.
Conclusion: In summary, EZH2 depletion overcame 5-FU resistance in GC by epigenetically silencing FBXO32, providing a novel therapeutic target for GC chemoresistance.

Keywords: gastric cancer, 5-FU, enhancer of zeste homologue 2, FBXO32

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