miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition

Cancer Genet. 2011 Sep;204(9):486-91. doi: 10.1016/j.cancergen.2011.07.004.

Abstract

microRNAs (miRNAs) play an important role in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In the current study, we defined the target genes and biological functions of miR-27 with a luciferase reporter assay and Western blot analysis. We verified that miR-27 levels were increased in gastric cancer tissues. The overexpression of miR-27 promoted the metastasis of AGS cells, whereas its depletion decreased cell metastasis. Up-regulation of miR-27 increased the levels of the epithelial-mesenchymal transition (EMT)-associated genes ZEB1, ZEB2, Slug, and Vimentin, as well as decreased E-cadherin levels. We demonstrated that miR-27 promoted EMT by activating the Wnt pathway. Finally, the APC gene was identified as the direct and functional target of miR-27. These results suggest an important role of miR-27 in regulating metastasis of gastric cancer and implicate the potential application of miR-27 in gastric cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, APC*
  • HEK293 Cells
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Middle Aged
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology
  • Phenotype
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Snail Family Transcription Factors
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Up-Regulation
  • Vimentin / genetics
  • Vimentin / metabolism
  • Wnt Signaling Pathway
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Cadherins
  • Homeodomain Proteins
  • MIRN27 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Repressor Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors
  • Vimentin
  • ZEB1 protein, human
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1