HDAC2 depletion promotes osteosarcoma’s stemness both in vitro and in vivo: a study on a putative new target for CSCs directed therapy

• DOI: 10.1186/s13046-018-0978-x
• Publication Date: 2018-12-03T08:43:54Z
• Authors: Marcella La Noce; Francesca Paino; Luigi Mele; Gianpaolo Papaccio; Tarik Regad; Angela Lombardi; Federica Papaccio; Vincenzo Desiderio; Virginia Tirino
• Keywords: Demethylating agent; Homeobox protein NANOG; Histone deacetylase 2

Cancer stem cells (CSCs) play a key role in cancer initiation, progression and chemoresistance. Epigenetic alterations have been identified as prominent factors that contribute to the CSCs phenotype. Here, we investigated effects of HDAC inhibitor valproic acid (VPA) demethylating agent, 5'azacytidine (DAC) on phenotype MG63 Saos2 osteosarcoma cell lines. were treated with DAC VPA, alone combination. Untreated examined for stemness by cytometry real-time PCR. Sarcospheres colonies formation also evaluated. Moreover, histone modification methylation tested flow cytomery western blotting. HDAC2 depleted their ability generate tumors NOD/SCID IL2R-gamma-0 (NSG) mice. expression human tissues was We found VPA induce an increased markers including CD133, OCT4, SOX2 NANOG, sarcospheres efficiency. Interestingly, showed treatment decreased repressive markers, while active ones. These modifications associated increase acetylation histones H3, decrease DNA global methylation, DNMT3a. Furthermore, silenced-MG63 acquired phenotype, promoted vivo tumorigenesis. In tissues, strongly expressed nucleus. Collectively, our results suggest expansion CSCs, report first time is factor regulating both growth. conclusion, potential therapeutic target treatment.