MiR-221-3p targets ARF4 and inhibits the proliferation and migration of epithelial ovarian cancer cells

Biochem Biophys Res Commun. 2018 Mar 18;497(4):1162-1170. doi: 10.1016/j.bbrc.2017.01.002. Epub 2017 Jan 3.

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. Although molecular diagnostic tools and targeted therapies have been developed over the past few decades, the survival rate is still rather low. Numerous researches suggest that some microRNAs (miRNAs) are key regulators of tumor progression. Among those miRNAs that has attracted much attention for their multiple roles in human cancers, the function of miR-221-3p in EOC has not been elucidated. Herein, we examined the expression of miR-221-3p in EOC patients and cell lines. Our data revealed that higher expression of miR-221-3p was linked to better overall survival in EOC patients. In-vitro experiments indicated that miR-221-3p inhibited EOC cell proliferation and migration. By performing subsequent systematic molecular biological and bioinformatic analyses, we found ADP-ribosylation factor (ARF) 4 is one of the putative target genes, the direct binding relationship was further confirmed by dual-luciferase reporter assay. Finally, a distinct gene expression between miR-221-3p and ARF4 in EOC group and normal group was identified, and the negative correlation between their expression levels in EOC specimens was further confirmed. Taken together, our research uncovered the tumor suppressive role of miR-221-3p in EOC and directly targeted ARF4, suggesting that miR-221-3p might be a novel potential candidate for clinical prognosis and therapeutics of EOC.

Keywords: ADP-Ribosylation factor 4; Cell migration; Cell proliferation; Epithelial ovarian cancer; Overall survival; microRNA-221-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / antagonists & inhibitors*
  • ADP-Ribosylation Factors / genetics
  • Adult
  • Carcinoma, Ovarian Epithelial
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • MicroRNAs / physiology*
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Survival Rate

Substances

  • MIRN221 microRNA, human
  • MicroRNAs
  • ADP-Ribosylation Factors
  • ARF4 protein, human