Integrated microarray meta-analysis identifies miRNA-27a as an oncogene in ovarian cancer by inhibiting FOXO1

Life Sci. 2018 Oct 1:210:263-270. doi: 10.1016/j.lfs.2018.08.043. Epub 2018 Aug 20.

Abstract

Aims: Survival of ovarian cancer patients is generally poor, partly because most of them are already at an advanced stage when diagnosed. The purpose of this study was to screen prognostic miRNAs for ovarian cancer, and to explore the underlying mechanisms.

Main methods: Integrated meta-analysis of miRNA microarrays retrieved from public repositories was employed to identify clinically significant miRNAs involved in ovarian cancer. Targets of candidate miRNA were predicted using four online databases, and validated with dual luciferase assay. Loss and gain of function were performed to investigate the role of miR27a in the growth of ovarian cancer cell lines.

Key findings: Based on cross-validation results in multiple datasets, we recognized hsa-miR-27a as an oncogenic molecular and a prognostic factor for ovarian cancer patients. Dual luciferase assay indicated tumor suppressor FOXO1 was a direct target of miR-27a. In addition, hsa-miR-27a could stimulate SKOV3 and A2780 cell proliferation and migration by regulating the expression of FOXO1.

Significance: In summary, our results indicate that miR-27a can promote progression of ovarian cancer by mediating FOXO1. To our knowledge, this is the first study focusing on the role of miR-27a/FOXO1 axis using the microarray meta-analysis in ovarian cancer. Furthermore, inhibiting miR-27a expression may be a new strategy for the treatment of ovarian cancer.

Keywords: FOXO1; Hsa-miR-27a; Integrated meta-analysis; Ovarian cancer; Prognosis.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Female
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Microarray Analysis
  • Oncogenes*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • MIRN27 microRNA, human
  • MicroRNAs