LncRNA ZEB1-AS1 down-regulation suppresses the proliferation and invasion by inhibiting ZEB1 expression in oesophageal squamous cell carcinoma

J Cell Mol Med. 2019 Dec;23(12):8206-8218. doi: 10.1111/jcmm.14692. Epub 2019 Oct 22.

Abstract

Multiple studies have unveiled that long non-coding RNAs (lncRNAs) play a pivotal role in tumour progression and metastasis. However, the biological role of lncRNA ZEB1-AS1 in oesophageal squamous cell carcinoma (ESCC) remains under investigation, and thus, the current study was to investigate the functions of ZEB1-AS1 in proliferation and invasion of ESCC. Here, we discovered that ZEB1-AS1 and ZEB1 were markedly up-regulated in ESCC tissues and cells relative to their corresponding normal control. ZEB1-AS1 and ZEB1 overexpressions were both related to TNM staging and lymph node metastasis as well as poor prognosis in ESCC. The hypomethylation of ZEB1-AS1 promoter triggered ZEB1-AS1 overexpression in ESCC tissues and cells. In addition, ZEB1-AS1 knockdown mediated by siRNA markedly suppressed the proliferation and invasion in vitro in EC9706 and TE1 cells, which was similar with ZEB1 siRNA treatment, coupled with EMT alterations including the up-regulation of E-cadherin level as well as the down-regulation of N-cadherin and vimentin levels. Notably, ZEB1-AS1 depletion dramatically down-regulated ZEB1 expression in EC9706 and TE1 cells, and ZEB1 overexpression obviously reversed the inhibitory effects of proliferation and invasion triggered by ZEB1-AS1 siRNA. ZEB1-AS1 shRNA evidently inhibited tumour growth and weight, whereas ZEB1 elevation partly recovered the tumour growth in ESCC EC9706 and TE1 xenografted nude mice. In conclusion, ZEB1-AS1 overexpression is tightly involved in the development and progression of ESCC, and it exerts the antitumour efficacy by regulating ZEB1 level in ESCC.

Keywords: Epithelial-mesenchymal transition; ZEB1; ZEB1-AS1; long non-coding RNA; oesophageal squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Down-Regulation*
  • Epithelial-Mesenchymal Transition / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / therapy
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / therapy
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNAi Therapeutics / methods
  • Xenograft Model Antitumor Assays / methods
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • RNA, Long Noncoding
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • long non-coding RNA ZEB1-AS1, human