Role of microRNAs in glucocorticoidresistant Bcell precursor acute lymphoblastic leukemia.
Oncol Rep
; 42(2): 708-716, 2019 Aug.
Article
em En
| MEDLINE
| ID: mdl-31233193
ABSTRACT
Acute lymphoblastic leukemia (ALL) is the most common malignant disorder in children and intensive combination therapy has markedly improved patient prognosis. However, efficacy of the treatment still fails in 1015% of patients. Glucocorticoids (GCs) such as prednisone and dexamethasone (DEX) are essential drugs used for ALL chemotherapy, and the response to GC treatment is a strong independent factor of ALL prognosis. In the present study, we examined the mechanism of GC resistance of Bcell precursor ALL (BCPALL). As determined by RTqPCR and western blot analyses, GC treatment upregulated glucocorticoid receptor (GR) protein and Bcl2interacting mediator of cell death (BCL2L11, BIM) protein expression, resulting in apoptosis of a GCsensitive BCPALL cell line, but not of a GCresistant BCPALL cell line as shown by flow cytometry. GR was downregulated in a DEXresistant BCPALL cell line which was induced by treatment of cells with increasing concentrations of DEX. Importantly, expression levels of miR1423p and miR17~92 cluster were upregulated in the BCPALL cell line with acquired DEX resistance as examined by RTqPCR. Our results suggest that interference of miR1423p and miR17~92 may overcome the resistance of BCPALL to GCs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia-Linfoma Linfoblástico de Células Precursoras B
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Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Resistencia a Medicamentos Antineoplásicos
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MicroRNAs
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Glucocorticoides
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article