MicroRNA-153 functions as a tumor suppressor by targeting SET7 and ZEB2 in ovarian cancer cells

Oncol Rep. 2015 Jul;34(1):111-20. doi: 10.3892/or.2015.3952. Epub 2015 May 5.

Abstract

The overall goal of the present study was to find and validate unidentified miRNAs that regulate epithelial-mesenchymal transition (EMT) and proliferation in ovarian cancer. Furthermore, we demonstrate that the high expression of miR-153 in human epithelial ovarian cancer (EOC) is associated with better survival. The mean expression level of miR-153 in ovarian cancer was significantly lower than in the adjacent carcinoma tissue. In the present study, we report that miR-153 are negative regulators of SET7 and ZEB2, miR-153 regulates SET7/ZEB2 expression and promotes SET7/ZEB2 mRNA degradation. Further, confirmed by reporter assays, SET7/ZEB2 are downstream targets of miR-153 directly bound to the 3' untranslated region (3'-UTR). Clone formation and wound-healing assay as well as Transwell assay proved that silencing of SET7 or ZEB2 partially abolished the enhancement of cell proliferation and invasion induced by downregulated miR-153. SET7 and ZEB2 are negatively correlated with miR-153 expression in human ovarian cancer and indicated a worse survival. Considering the role of SET7 and ZEB2 in EOC, it is important to clarify how the expression of SET7 and ZEB2 are regulated. Based on our results miR-153 inhibits proliferation and suppresses EMT and the invasive potential of ovarian cancer cells through downregulation of SET7 and ZEB2, supporting the pursuit of miR-153 as a potential target for ovarian cancer intervention.

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histone-Lysine N-Methyltransferase / biosynthesis*
  • Histone-Lysine N-Methyltransferase / genetics
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / genetics
  • Zinc Finger E-box Binding Homeobox 2

Substances

  • 3' Untranslated Regions
  • Homeodomain Proteins
  • MIRN153 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • Histone-Lysine N-Methyltransferase
  • SETD7 protein, human