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
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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]