MicroRNA-219-5p inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells by targeting the Twist/Wnt/β-catenin signaling pathway

Gene. 2017 Dec 30:637:25-32. doi: 10.1016/j.gene.2017.09.012. Epub 2017 Sep 7.

Abstract

MicroRNAs are emerging as critical regulators in various fundamental biological processes, including tumor progression. MicroRNA-219-5p (miR-219-5p) has been suggested as a novel tumor suppressing miRNA for many types of human cancers. However, the expression and functional significance of miR-219-5p in epithelial ovarian cancer remain poorly understood. In this study, we sought to explore the potential functions of miR-219-5p in epithelial ovarian cancer. Herein, we found that miR-219-5p levels were significantly decreased in epithelial ovarian cancer tissues and cell lines. Further experiments showed that overexpression of miR-219-5p inhibited epithelial ovarian cancer cell proliferation, migration, and invasion, and suppressed the Wnt/β-catenin signaling pathway. By contrast, suppression of miR-219-5p exhibited the opposite effects. Twist was identified as a downstream target of miR-219-5p, and its expression was directly regulated by miR-219-5p. Restoration of Twist expression in miR-219-5p-overexpresing cells significantly reversed the antitumor effects of miR-219-5p. Taken together, our results revealed a tumor suppressive role for miR-219-5p in epithelial ovarian cancer that includes suppression of cell proliferation, migration, and invasion through downregulation of the Twist/Wnt/β-catenin signaling pathway. Our study suggests that miR-219-5p may have potential applications in the diagnosis and treatment of epithelial ovarian cancer.

Keywords: Epithelial ovarian cancer; Twist; Wnt; miR-219-5p.

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Carcinoma, Ovarian Epithelial
  • Cell Movement*
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • MIRN219 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • Wnt Proteins
  • beta Catenin