miR-146a-5p mediates epithelial-mesenchymal transition of oesophageal squamous cell carcinoma via targeting Notch2

Br J Cancer. 2016 Dec 6;115(12):1548-1554. doi: 10.1038/bjc.2016.367. Epub 2016 Nov 10.

Abstract

Background: Our previous study found that dysregulated microRNA-146a-5p (miR-146a-5p) is involved in oesophageal squamous cell cancer (ESCC) proliferation. This article aimed to evaluate its detailed mechanisms in ESCC epithelial-mesenchymal transition (EMT) progression.

Methods: Invasion assay, qRT-PCR and western blotting were used to validate the roles of miR-146a-5p and Notch2 in EMT progression. miRNA target gene prediction databases and dual-luciferase reporter assay were used to validate the target gene.

Results: miR-146a-5p inhibitor led to increase of invaded ESCC cells, while miR-146a-5p mimics inhibited invasion ability of ESCC cells. Protein level of E-cadherin decreased, whereas those of Snail and Vimentin increased in the anti-miR-146a-5p group, which demonstrated that miR-146a-5p inhibits EMT progression of ESCC cells. miRNA target gene prediction databases indicated the potential of Notch2 as a direct target gene of miR-146a-5p and dual-luciferase reporter assay validated it. Importantly, shRNA-Notch2 restrained EMT and partially abrogated the inhibiting effects of miR-146a-5p on EMT progression of ESCC cells.

Conclusions: miR-146a-5p functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the EMT progression of ESCC.

MeSH terms

  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / physiology*
  • Esophageal Neoplasms / pathology*
  • Humans
  • MicroRNAs / physiology*
  • Receptor, Notch2 / physiology*

Substances

  • MIRN146 microRNA, human
  • MicroRNAs
  • NOTCH2 protein, human
  • Receptor, Notch2