Simultaneous downregulation of miR-21 and miR-155 through oleuropein for breast cancer prevention and therapy

J Cell Biochem. 2018 Sep;119(9):7151-7165. doi: 10.1002/jcb.26754. Epub 2018 Jun 15.

Abstract

Breast cancer (BC) is the leading cause of cancer mortality in women worldwide. It recently was proven that miRNAs play a critical role in BC development. The use of natural agents for control of cancer by modulating miRNAs is promising. Oleuropein is a natural polyphenolic agent with anti-neoplastic properties and is well tolerated by humans. This study was undertaken to determine the therapeutic effects of oleuropein through modulation of master oncomiRs (miR-21 and miR-155) in BC cells. The present study provides the first link between miRNA and oleuropein as a mechanism in BC. MCF-7 cells were tested with and without oleuropein and the cell viability, apoptosis, and migration were examined. The effect of oleuropein on miR-21 and miR-155 expression was assessed through qRT-PCR. It was found that oleuropein induced apoptosis and retarded cell migration and invasion in a dose-dependent manner in the human MCF7 BC cell line. It was observed that oleuropein significantly decreased expression of both miR-21 and miR-155 over time in a dose-dependent manner. These results demonstrate that oleuropein is a potential therapeutic and preventive agent for BC. Oleuropein exhibits an anti-cancer effect by modulation of tumor suppressor gene expression, which is targeted by oncomiRs.

Keywords: anti-cancer effect; breast cancer; miR-155; miR-21; miRNA; oleuropein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / prevention & control*
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Iridoid Glucosides
  • Iridoids / therapeutic use*
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / prevention & control

Substances

  • Iridoid Glucosides
  • Iridoids
  • MIRN155 microRNA, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • oleuropein