Knockdown of lncRNA ZEB2NAT suppresses epithelial mesenchymal transition, metastasis and proliferation in breast cancer cells

Gene. 2021 Dec 30:805:145904. doi: 10.1016/j.gene.2021.145904. Epub 2021 Aug 19.


Breast cancer is the second most common cause of cancer-related mortality in women. Breast cancer metastasis which usually is observed at the last stage is the major cause of breast cancer-related death. Long non-coding RNAs (lncRNAs) are member of the non-coding RNA family. It is known that lncRNAs have important functions in the genes regulation of different processes and pathways such as EMT (Epithelial mesenchymal transition), metastasis and apoptosis. Therefore, it is inevitable that lncRNAs have potential contribution for the understanding of cancer pathogenesis. lncRNA-ZEB2NAT is the natural antisense transcript of ZEB2. Herein, we investigated the effects of lncRNA-ZEB2NAT on process of EMT, metastasis and apoptosis in MCF7 and MDA-MB-231 breast cancer cells. The effect of ZEB2NAT on the expression of important genes in EMT, metastasis and apoptosis, and some protein levels was determined by qRT-PCR and western blot analysis, respectively. The effects of ZEB2NAT on cell proliferation, apoptosis, invasion and colony formation were evaluated using XTT, annexin V, invasion and colony assays, respectively. The ZEB2NAT knockdown caused anti-metastatic and apoptotic effects. The ZEB2NAT knockdown resulted in a decrease in ZEB2 and N-cadherin but an increase in E-cadherin protein levels. In addition, it was determined that ZEB2NAT knockdown significantly decreased cell proliferation and stimulated apoptosis in both cells. It was found that ZEB2NAT knockdown significantly decreased invasion and colony formation in both cells. ZEB2NAT knockdown showed anti-metastatic and apoptotic effect by affecting the important genes in both cells. These results have suggested that ZEB2NAT has an important role in EMT, metastasis and apoptosis in breast cancer and ZEB2NAT knockdown caused significant anti-cancer activities.

Keywords: Apoptosis; Breast cancer; EMT; Metastasis; ZEB2NAT.

MeSH terms

  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics
  • RNA, Long Noncoding / genetics
  • Zinc Finger E-box Binding Homeobox 2 / genetics*
  • Zinc Finger E-box Binding Homeobox 2 / metabolism


  • Cadherins
  • RNA, Long Noncoding
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2