Genistein down-regulates miR-223 expression in pancreatic cancer cells

Curr Drug Targets. 2013 Sep;14(10):1150-6. doi: 10.2174/13894501113149990187.

Abstract

Although genistein has been shown to inhibit tumorigenesis in a variety of human cancers including pancreatic cancer (PC), the exact molecular mechanism of its anti-cancer effects has not yet been fully elucidated. Recently, microRNAs (miRNAs) have been reported to regulate multiple aspects of tumor development and progression, indicating that targeting miRNAs could be a novel strategy to treat human cancers. In the current study, we investigated whether a natural compound genistein could down-regulate onco-miR-223, resulting in the inhibition of cell growth and invasion, and induction of apoptosis in PC cells. We found that genistein treatment significantly inhibited miR-223 expression and up-regulated Fbw7, one of the targets of miR-223. Moreover, down-regulation of miR-223 inhibited cell growth and induced apoptosis in PC cells. These findings suggest that genistein exerts its anti-tumor activity partly through downregulation of miR-223 in PC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation
  • F-Box Proteins / genetics*
  • F-Box Proteins / metabolism
  • F-Box-WD Repeat-Containing Protein 7
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genistein / pharmacology*
  • Genistein / therapeutic use
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • MIRN223 microRNA, human
  • MicroRNAs
  • Genistein
  • Ubiquitin-Protein Ligases