title: Histone Deacetylase Inhibitors Repress Tumoral Expression of the Proinvasive Factor RUNX2.
abstract: Aberrant reactivation of embryonic pathways occurs commonly in cancer. The transcription factor RUNX2 plays a fundamental role during embryogenesis and is aberrantly reactivated during progression and metastasization of different types of human tumors. In this study, we attempted to dissect the molecular mechanisms governing RUNX2 expression and its aberrant reactivation. We identified a new regulatory enhancer element, located within the RUNX2 gene, which is responsible for the activation of the RUNX2 promoter and for the regulation of its expression in cancer cells. Furthermore, we have shown that treatment with the anticancer compounds histone deacetylase inhibitor (HDACi) results in a profound inhibition of RUNX2 expression, which is determined by the disruption of the transcription-activating complex on the identified enhancer. These data envisage a possible targeting strategy to counteract the oncongenic function of RUNX2 in cancer cells and provide evidence that the cytotoxic activity of HDACi in cancer is not only dependent on the reactivation of silenced oncosuppressors but also on the repression of oncogenic factors that are necessary for survival and progression.
authors.affiliation: Laboratory of Translational Research, Research and Statistic Infrastructure, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy. Alessia.Ciarrocchi@asmn.re.it Valentina.Sancisi@asmn.re.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sancisi
authors.affiliation: Laboratory of Translational Research, Research and Statistic Infrastructure, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Gandolfi
authors.affiliation: Laboratory of Molecular Biology, Department of Pharmacology and Biotechnology (FaBiT), University of Bologna, Bologna, Italy.
authors.forename: Davide Carlo
authors.initials: DC
authors.lastname: Ambrosetti
authors.affiliation: Laboratory of Translational Research, Research and Statistic Infrastructure, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy. Alessia.Ciarrocchi@asmn.re.it Valentina.Sancisi@asmn.re.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciarrocchi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D050659:Core Binding Factor Alpha 1 Subunit; D056572:Histone Deacetylase Inhibitors; C493709:RUNX2 protein, human; D006655:Histone Deacetylases