MicroRNA-200c inhibits the metastasis of non-small cell lung cancer cells by targeting ZEB2, an epithelial-mesenchymal transition regulator

Mol Med Rep. 2016 Apr;13(4):3349-55. doi: 10.3892/mmr.2016.4901. Epub 2016 Feb 17.

Abstract

MicroRNAs (miRs) have been demonstrated to regulate various biological processes in human cancer, including non-small cell lung cancer (NSCLC). However, little evidence has been provided regarding the exact role of miR-200c in mediating the malignant progression of NSCLC, as well as the underlying mechanism. The present study aimed to investigate the putative role of miR‑200c in the progression of NSCLC. The expression levels of miR‑200c were significantly reduced in NSCLC cell lines compared with in normal lung epithelial cells, as determined by reverse transcription‑quantitative polymerase chain reaction. Overexpression of miR‑200c significantly suppressed cell migration and invasion of A549 NSCLC cells. Results of a luciferase reporter assay further identified zinc finger E‑box‑binding homeobox 2 (ZEB2) as a direct target gene of miR‑200c, and the expression of ZEB2 was shown to be suppressed in A549 cells overexpressing miR‑200c. Furthermore, small interfering RNA‑mediated inhibition of ZEB2 suppressed the migration and invasion of A549 cells. In addition, since ZEB2 is an epithelial‑mesenchymal transition (EMT) regulator, the role of miR‑200c in the regulation of EMT in NSCLC cells was further examined. Results of a western blot analysis indicated that overexpression of miR‑200c upregulated E‑cadherin, and downregulated N‑cadherin and vimentin expression in A549 cells, thus suggesting that EMT was suppressed. Based on these results, the present study suggested that miR‑200c was able to inhibit the metastasis of NSCLC cells by targeting ZEB2. Therefore, miR-200c may be considered as a potential candidate for the treatment of NSCLC.

Publication types

  • Retracted Publication

MeSH terms

  • 3' Untranslated Regions
  • A549 Cells
  • Base Sequence
  • Cadherins / metabolism
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Movement
  • Down-Regulation
  • Epithelial-Mesenchymal Transition*
  • Genes, Reporter
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oligonucleotides, Antisense / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Up-Regulation
  • Vimentin / metabolism
  • Zinc Finger E-box Binding Homeobox 2

Substances

  • 3' Untranslated Regions
  • Cadherins
  • Homeodomain Proteins
  • MicroRNAs
  • Oligonucleotides, Antisense
  • RNA, Small Interfering
  • Repressor Proteins
  • Vimentin
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2