miR-143 interferes with ERK5 signaling, and abrogates prostate cancer progression in mice

PLoS One. 2009 Oct 26;4(10):e7542. doi: 10.1371/journal.pone.0007542.

Abstract

Background: Micro RNAs are small, non-coding, single-stranded RNAs that negatively regulate gene expression at the post-transcriptional level. Since miR-143 was found to be down-regulated in prostate cancer cells, we wanted to analyze its expression in human prostate cancer, and test the ability of miR-43 to arrest prostate cancer cell growth in vitro and in vivo.

Results: Expression of miR-143 was analyzed in human prostate cancers by quantitative PCR, and by in situ hybridization. miR-143 was introduced in cancer cells in vivo by electroporation. Bioinformatics analysis and luciferase-based assays were used to determine miR-143 targets. We show in this study that miR-143 levels are inversely correlated with advanced stages of prostate cancer. Rescue of miR-143 expression in cancer cells results in the arrest of cell proliferation and the abrogation of tumor growth in mice. Furthermore, we show that the effects of miR-143 are mediated, at least in part by the inhibition of extracellular signal-regulated kinase-5 (ERK5) activity. We show here that ERK5 is a miR-143 target in prostate cancer.

Conclusions: miR-143 is as a new target for prostate cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Computational Biology / methods
  • Disease Progression
  • Electroporation
  • Humans
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinase 7 / metabolism*
  • Prostatic Neoplasms / metabolism*
  • Signal Transduction*

Substances

  • MIRN143 microRNA, human
  • MicroRNAs
  • MIRN143 microRNA, mouse
  • Mitogen-Activated Protein Kinase 7