Inhibition of splicing factors SF3A3 and SRSF5 contributes to As3+/Se4+ combination-mediated proliferation suppression and apoptosis induction in acute promyelocytic leukemia cells.
Arch Biochem Biophys
; 743: 109677, 2023 07 15.
Article
en En
| MEDLINE
| ID: mdl-37356608
ABSTRACT
The low-dose combination of Arsenite (As3+) and selenite (Se4+) has the advantages of lower biological toxicity and better curative effects for acute promyelocytic leukemia (APL) therapy. However, the underlying mechanisms remain unclear. Here, based on the fact that the combination of 2 µM A3+ plus 4 µM Se4+ possessed a stronger anti-leukemic effect on APL cell line NB4 as compared with each individual, we employed iTRAQ-based quantitative proteomics to identify a total of 58 proteins that were differentially expressed after treatment with As3+/Se4+ combination rather than As3+ or Se4+ alone, the majority of which were involved in spliceosome pathway. Among them, eight proteins stood out by virtue of their splicing function and significant changes. They were validated as being decreased in mRNA and protein levels under As3+/Se4+ combination treatment. Further functional studies showed that only knockdown of two splicing factors, SF3A3 and SRSF5, suppressed the growth of NB4 cells. The reduction of SF3A3 was found to cause G1/S cell cycle arrest, which resulted in proliferation inhibition. Moreover, SRSF5 downregulation induced cell apoptosis through the activation of caspase-3. Taken together, these findings indicate that SF3A3 and SRSF5 function as pro-leukemic factors and can be potential novel therapeutic targets for APL.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_leukemia
Asunto principal:
Leucemia Promielocítica Aguda
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Arch Biochem Biophys
Año:
2023
Tipo del documento:
Article