MicroRNA-125b Suppresses Ovarian Cancer Progression via Suppression of the Epithelial-Mesenchymal Transition Pathway by Targeting the SET Protein

Cell Physiol Biochem. 2016;39(2):501-10. doi: 10.1159/000445642. Epub 2016 Jul 7.

Abstract

Background/aims: MicroRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to chemotherapy resistance. However, its role in epithelial ovarian carcinoma remains unknown. The goal of this study was to identify the relationship between miR-125b and the epithelial-mesenchymal transition (EMT) in ovarian cancer.

Methods: In total, 55patients with epithelial ovarian cancer (EOC) were included in our study. The relative expression of miR-125b was measured using real-time polymerase chain reaction (RT-PCR).The protein expression of SET and EMT-related indicators in cell lines were assessed by Western blot. The regulation of SET by miR-125b was confirmed using luciferase reporter assays. The effect of miR-125b on metastasis was evaluated using an in vivo metastasis model.

Results: miR-125b expression was markedly lower in the EOC specimens. Ectopic expression of miR-125b in EOC cells significantly inhibited tumor invasion.miR-125b expression was negatively associated with both EMT and SET expression, in vivo and in vitro. Mechanistic studies identified SET as a direct target of miR-125b, and the downregulation of SET, observed during tumor migration, was affected by the overexpression of miR125b.

Conclusion: miR-125b suppresses EOC cell migration and invasion by targeting the SET protein, and this study may provide a novel mechanism for understanding the progression of EOC.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Blotting, Western
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Movement / genetics
  • DNA-Binding Proteins
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Histone Chaperones / genetics*
  • Histone Chaperones / metabolism
  • Humans
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Signal Transduction / genetics
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transplantation, Heterologous

Substances

  • 3' Untranslated Regions
  • DNA-Binding Proteins
  • Histone Chaperones
  • MIRN125 microRNA, human
  • MicroRNAs
  • SET protein, human
  • Transcription Factors