Interferon alpha-inducible protein 27 promotes epithelial-mesenchymal transition and induces ovarian tumorigenicity and stemness

J Surg Res. 2015 Jan;193(1):255-64. doi: 10.1016/j.jss.2014.06.055. Epub 2014 Jul 5.

Abstract

Background: Interferon alpha-inducible protein 27 (IFI27) is an interferon alpha-inducible protein, which was found to be upregulated in some cancers, such as breast cancer, squamous cell carcinoma, hepatocellular carcinoma, and serous ovarian carcinoma. However, the role of IFI27 in ovarian cancer remains to be elucidated. This study was designed to investigate the role of IFI27 in ovarian cancer tumorigenicity.

Materials and methods: The expression of IFI27 was examined in ovarian cancer tissues and cell lines by real time quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The cell migration and invasion was investigated by wound healing and transwell invasion assay. The epithelial-mesenchymal transition markers were detected by Western blotting and the stemness was evaluated by sphere formation. The tumor growth was examined in the athymic mice model.

Results: We found that IFI27 is overexpressed in ovarian cancer and associated with patients' survival. Interestingly, we further observed that the expression of IFI27 was associated with the expression of mesenchymal marker vimentin in ovarian cancer. Overexpression of IFI27 induces epithelial-mesenchymal transition and promotes epithelial ovarian cancer cells migration and invasion, tumorigenicity, stemness, and drug resistance. Moreover, overexpression of IFI27 is associated with loss of miR-502 in ovarian cancer. Reexpression of miR-502 inhibits IFI27-induced tumorigenicity, migration, and drug resistance.

Conclusions: These data suggested that IFI27 may be a potential target for developing novel diagnosis strategies and therapeutic interventions.

Keywords: Epithelial–mesenchymal transition; IFI27; Metastasis; Ovarian cancer; miR-502.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon-alpha / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Ovarian Neoplasms / pathology*
  • Vimentin / metabolism

Substances

  • Biomarkers, Tumor
  • IFI27 protein, human
  • Interferon-alpha
  • MIRN502 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Vimentin