MicroRNA-433 inhibits migration and invasion of ovarian cancer cells via targeting Notch1

Neoplasma. 2016;63(5):696-704. doi: 10.4149/neo_2016_506.

Abstract

We aimed to determine the effects of miR-433 on the malignant behaviors of ovarian cancer cells, as well as to elucidate the possible mechanisms of ovarian cancer development. A total of 9 ovarian cancer tissues and 9 matched normal ovary tissues were obtained, and the expression levels of miR-433 and Notch1 were then determined by real-time PCR. Human ovarian cancer cell lines SKOV3 and OVCAR3 were transfected with miR-433 mimics, negative miR-control and Notch1 siRNA. The expression of Notch1 protein in transfected cells was determined by western blot. In addition, the proliferation, migration and invasion of SKOV3 and OVCAR3 cells in vitro were then evaluated using Cell Counting Kit 8, wound healing assay and Transwell invasion assay, respectively. Besides, bioinformatics methods and luciferace reporter assay were performed to confirm whether Notch1 was a direct target of miR-433. The expression of miR-433 was markedly down-regulated while Notch1 expression was significantly up-regulated in ovarian cancer tissues compared with matched normal ovary tissues. Overexpression of miR-433 significantly inhibited the migration and invasion of ovarian cancer cells, but had not significant effects on cell proliferation. In addition, Notch1 was a direct target of miR-433. Besides, down-regulation of Notch1 inhibited the invasion of ovarian cancer cells. Our findings indicate that miR-433 may inhibit cell migration and invasion in the development of ovarian cancer via down-regulation of Notch1. Notch1 may serve as a potential target in cancer therapy.

Keywords: Notch1; invasion.; miR-433; migration; ovarian cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Female
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • RNA, Small Interfering / genetics
  • Receptor, Notch1 / biosynthesis*
  • Receptor, Notch1 / genetics

Substances

  • MIRN433 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • RNA, Small Interfering
  • Receptor, Notch1