Título:	Epigenetic priming by EHMT1/EHMT2 in acute lymphoblastic leukemia induces TP53 and TP73 overexpression and promotes cell death
Autor(es):	Carvalho, Amandda Évelin Silva Alencar, Ana Paula Dorneles Resende, Marielly Reis Costa, Daniel Freitas da Nonino, Alexandre Neves, Francisco Assis Rocha Araujo, Felipe Saldanha de
Assunto:	Leucemia linfoblástica aguda (LLA) Epigenética
Data de publicação:	2020
Editora:	Elsevier Ltd.
Referência:	CARVALHO, Amandda Évelin Silva et al. Epigenetic priming by EHMT1/EHMT2 in acute lymphoblastic leukemia induces TP53 and TP73 overexpression and promotes cell death. Toxicology in Vitro, v. 69, dez. 2020, 104992. DOI: https://doi.org/10.1016/j.tiv.2020.104992. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0887233320305427.
Abstract:	Euchromatic histone-lysine N-methyltransferase 1 (EHMT1) and EHMT2 are upregulated in various human cancers, and their deregulation is associated with tumor development and progression. In this paper, we investigated the expression level of EHMT1/EHMT2 in acute lymphoblastic leukemia (ALL) and whether the modulation of these enzymes could have any cellular or molecular impact on ALL cells. For this, we used UNC0646 as a priming strategy to target EHMT1/EHMT2 and investigated its effect on proliferation and cell viability of Jurkat cells by MTT assay. Then, considering the IC50 and IC75, cellular death was determined by Annexin V/PI staining using flow cytometry. Finally, we investigated by RT-PCR the molecular bases that could be involved in the observed effects. Interestingly, accessing the International Microarray Innovations in Leukemia (MILE) study group, we detected that both EHMT1 and EHMT2 are overexpressed in ALL. More important, we determined that inhibition of EHMT1/EHMT2 significantly decreased Jurkat cell viability in a dose-dependent manner. Accordingly, we observed that inhibition of EHMT1/EHMT2 promoted Jurkat cell death, which was accompanied by increased expression of P53, TP73, BAX, and MDM4. These results clearly indicate that inhibition of EHMT1/EHMT2 induces pro-apoptotic gene expression in ALL and promotes cell death. More importantly, the modulation of these histone methyltransferases may be a promising epigenetic target for ALL treatment.
DOI:	https://doi.org/10.1016/j.tiv.2020.104992
Versão da editora:	https://www.sciencedirect.com/science/article/abs/pii/S0887233320305427
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