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

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

Author information

1
Biomedical Applications Unit, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 116 35 Athens, Greece.
2
Centre of Systems Biology, Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Str., 11527 Athens, Greece.
3
Laboratory of Histology-Embryology, Molecular Carcinogenesis Group, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
4
Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
5
Regional Center for Applied and Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
6
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.

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

PMID:
27919789
DOI:
10.1016/j.canlet.2016.11.036
[Indexed for MEDLINE]

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