title: Unravelling a p73-regulated network: The role of a novel p73-dependent target, MIR3158, in cancer cell migration and invasiveness.
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.
authors.affiliation: Biomedical Applications Unit, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 116 35 Athens, Greece.
authors.forename: Sotiris
authors.initials: S
authors.lastname: Galtsidis
authors.affiliation: Biomedical Applications Unit, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 116 35 Athens, Greece.
authors.forename: Stella
authors.initials: S
authors.lastname: Logotheti
authors.affiliation: Centre of Systems Biology, Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Str., 11527 Athens, Greece.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Pavlopoulou
authors.affiliation: Laboratory of Histology-Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Christos P
authors.initials: CP
authors.lastname: Zampetidis
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Papachristopoulou
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.affiliation: Regional Center for Applied and Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Borek
authors.initials: B
authors.lastname: Vojtesek
authors.affiliation: Laboratory of Histology-Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Gorgoulis
authors.affiliation: Biomedical Applications Unit, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 116 35 Athens, Greece. Electronic address: vzub@eie.gr.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Zoumpourlis
mesh_terms: D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics*; D014162:Transfection; D000072160:Tumor Protein p73 / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D000072160:Tumor Protein p73
keywords: Anticancer targeting; Epithelial–mesenchymal transition; MIR3158; MIR34A; p73