| Texto completo | |
| Autor(es): |
Farias, Jessica O.
;
Pacheco, Diana R. D. C. G.
;
Magalhaes, Yuli T.
;
Russo, Lilian C.
;
Boell, Viktor K.
;
Hilares, Donna J. F.
;
Forti, Fabio L.
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | TISSUE & CELL; v. 96, p. 11-pg., 2025-10-01. |
| Resumo | |
Dual-specificity phosphatase 3 (DUSP3) regulates key cellular processes, including the cell cycle, proliferation, and differentiation. Recently, we demonstrated its crucial role in maintaining genomic stability by interacting with and dephosphorylating nucleophosmin (NPM), thereby modulating nuclear p53 activity under genotoxic stress. Given the frequent mutations in both p53 and NPM in acute myeloid leukemia (AML), this study aimed to investigate the impact of DUSP3 knockdown in two p53-deficient AML cell lines and explore potential correlations with NPM expression. THP-1 cells exhibited higher basal levels of DUSP3 and NPM compared to HL-60 cells, while DUSP3 knockdown reduced NPM expression in HL-60 cells. Upon phorbol 12-myristate 13-acetate (PMA)-induced differentiation into macrophage-like cells, only HL-60 cells displayed decreased levels of both DUSP3 and NPM. DUSP3 knockdown enhanced differentiation in THP-1 and HL-60 cells and promoted nonclassical M2 macrophage polarization following additional PMA exposure, as indicated by increased expression of CD11b and CD206. Bioinformatics analysis revealed significant correlations between DUSP3 and NPM gene expression, AML patient survival, and the maturation stage of myeloid cells. Furthermore, DUSP3 knockdown in undifferentiated HL-60 cells impaired proliferation and compromised genomic stability under genotoxic stress induced by doxorubicin. These findings suggest that DUSP3 plays a regulatory role in the differentiation, polarization, and proliferation of myeloid cells. Through the modulation of NPM expression and activity, DUSP3 may contribute to a deeper understanding of leukemia pathophysiology and mechanisms of chemotherapy resistance. (AU) | |
| Processo FAPESP: | 15/03983-0 - Investigação molecular e funcional da interação de DUSP3 com proteínas nucleares: implicações em mecanismos de reparo de DNA |
| Beneficiário: | Fábio Luis Forti |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 18/01753-6 - Identificação e investigação funcional de proteínas que interagem com as enzimas Cdc42 e DUSP12 em células humanas sob condições de instabilidade genômica: uma abordagem proteômica |
| Beneficiário: | Fábio Luis Forti |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 17/16491-4 - Avaliação das proteínas VHR e NPM no reparo de DNA e proliferação de células leucêmicas |
| Beneficiário: | Jessica Oliveira Farias |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 22/04243-4 - Avaliação funcional e molecular da fosfatase DUSP12 em células tumorais humanas submetidas a condições de estresse |
| Beneficiário: | Fábio Luis Forti |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |