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Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Esophageal Cancer | Primary research

LINC00152 upregulates ZEB1 expression and enhances epithelial-mesenchymal transition and oxaliplatin resistance in esophageal cancer by interacting with EZH2

Authors: Shuyao Zhang, Wei Liao, Qinshui Wu, Xiaoshan Huang, Zhen Pan, Wang Chen, Shuyi Gu, Zuojun Huang, Yiwen Wang, Xu Tang, Shanshan Liang, Xiaoyan Zhang, Yun Chen, Shuang Chen, Wanying Chen, Yi Jiang, Chen Chen, Guodong Qiu

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Expression of the long non-coding mRNA LINC00152 has been reported to correlate with cancer cell resistance to oxaliplatin (L-OHP). However, little is known regarding the molecular mechanism of LINC00152 in esophageal cancer (EC). Hence, we intended to characterize the role of LINC00152 in EC, with a special focus on epithelial-mesenchymal transition (EMT) and L-OHP resistance.

Methods

We collected EC tissues and identified EC cell lines with higher L-OHP resistance, and then characterized expression patterns of LINC00152, Zeste Homologue 2 (EZH2), Zinc finger e-box binding homeobox (ZEB1) and EMT-related genes using RT-qPCR and Western blot analysis. Furthermore, their functional significance was identified by gain and loss-of-function experiments. The relationship among LINC00152, EZH2 and ZEB1 was examined using RIP, RNA pull-down and ChIP assays. Additionally, resistance of EC cells to L-OHP was reflected by CCK-8 assay to detect cell viability. Animal experiments were also conducted to detect the effects of the LINC00152/EZH2/ZEB1 on EMT and L-OHP resistance.

Results

LINC00152, EZH2 and ZEB1 were highly expressed in EC tissues and Kyse−150/TE-1 cells. As revealed by assays in vitro and in vivo, LINC00152 positively regulated ZEB1 expression through interaction with EZH2 to enhance EMT and L-OHP resistance in EC cells. In contrast, silencing of LINC00152 contributed to attenuated EMT and drug resistance of EC cells to L-OHP.

Conclusions

Our study demonstrates that LINC00152/EZH2/ZEB1 axis can regulate EMT and resistance of EC cells to L-OHP, thus presenting a potential therapeutic target for EC treatment.
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Metadata
Title
LINC00152 upregulates ZEB1 expression and enhances epithelial-mesenchymal transition and oxaliplatin resistance in esophageal cancer by interacting with EZH2
Authors
Shuyao Zhang
Wei Liao
Qinshui Wu
Xiaoshan Huang
Zhen Pan
Wang Chen
Shuyi Gu
Zuojun Huang
Yiwen Wang
Xu Tang
Shanshan Liang
Xiaoyan Zhang
Yun Chen
Shuang Chen
Wanying Chen
Yi Jiang
Chen Chen
Guodong Qiu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01620-1

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