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

Galtsidis S., Logotheti S., Pavlopoulou A., Zampetidis C. P., Papachristopoulou G., Scorilas A., ...Daha Fazla

CANCER LETTERS, cilt.388, ss.96-106, 2017 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 388
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.canlet.2016.11.036
  • Dergi Adı: CANCER LETTERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.96-106
  • Anahtar Kelimeler: p73, MIR3158, MIR34A, Epithelial-mesenchymal transition, Anticancer targeting, BREAST-CANCER, MESENCHYMAL TRANSITION, TRANSCRIPTION FACTORS, P53 NETWORK, P73, MICRORNAS, EXPRESSION, GENES, TAP73, METASTASIS
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

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/beta-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/beta-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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.