Unravelling a p73-regulated network: The role of a novel p73-dependent target, MIR3158, in cancer cell migration and invasiveness

Cancer Lett. 2017 Mar 1;388:96-106. doi: 10.1016/j.canlet.2016.11.036. Epub 2016 Dec 3.

Abstract

The transcription factor p73 is homologous to the well-known tumor-suppressor p53. The p73-regulated networks are of significant clinical interest, because they may substitute for impaired p53-regulated networks which are commonly perturbed in cancer. Herein, we aimed to characterize a p73-regulated network that mediates cell migration and restores anti-oncogenic responses in p53-mutant cancer cells. In this study, we demonstrate that p73 regulates a network underlying cell migration, which consists of MIR34A/MIR3158/vimentin/β-catenin/lef1. The p73 isoforms transactivate the miRNA components (MIR34A/MIR3158) of this network, which in turn, downregulate their EMT-related mRNA co-targets (vimentin/β-catenin/lef1) to decrease cell-migration. Modulation of this network, by increasing the level of the novel p73-dependent target MIR3158, was found to induce anti-oncogenic/anti-invasive responses in p53-mutant cancer cells. Taken together, a p73-regulated, MIR3158-containing, network restores anti-invasive phenotypes in p53-mutant cancer cells; this property could be exploited towards the development of anticancer therapeutics.

Keywords: Anticancer targeting; Epithelial–mesenchymal transition; MIR3158; MIR34A; p73.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement
  • Epithelial-Mesenchymal Transition / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Osteosarcoma / genetics*
  • Transfection
  • Tumor Protein p73 / genetics*

Substances

  • MicroRNAs
  • Tumor Protein p73