Cancer Cell International (Nov 2020)

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

  • 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

DOI
https://doi.org/10.1186/s12935-020-01620-1
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 14

Abstract

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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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