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MiR-124 contributes to glucocorticoid resistance in acute lymphoblastic leukemia by promoting proliferation, inhibiting apoptosis and targeting the glucocorticoid receptor
- Source :
- The Journal of steroid biochemistry and molecular biology. 172
- Publication Year :
- 2016
-
Abstract
- Acute lymphoblastic leukemia (ALL) is characterized by the accumulation of abnormal lymphoblasts in the bone marrow and blood. Though great progress has been made for improvement in clinical treatment during the past decades, some children with ALL still relapsed. Glucocorticoid (GC) resistance is an important clinical problem for ALL treatment failure. Therefore, further understanding of the mechanism of GC resistance and exploring novel therapeutic strategies are crucial for improving treatment outcome. The reported involvement of microRNAs (miRNAs) in drug resistance implied that deregulated miRNA expression might contribute to GC treatment response of ALL. However, individual miRNAs and their functional mechanisms potentially involved in the GC response are still largely unknown. In the present study, we found that miR-124 was up-regulated in prednisone insensitive human ALL cell line and prednisone-poor response ALL patients. Furthermore, it was found that miR-124 might contribute to GC resistance by promoting proliferation and inhibiting apoptosis of ALL cells. Importantly, we validated that miR-124, targeted and decreased the expression of glucocorticoid receptor (NR3C1), prevented the inhibitory effect of GC in ALL. These findings strongly suggest that miR-124 is critical in poor GC response and may serve as a potential therapeutic target in ALL with poor GC resistance.
- Subjects :
- 0301 basic medicine
Male
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Apoptosis
Bone Marrow Cells
Drug resistance
Biology
Pharmacology
Biochemistry
Dexamethasone
03 medical and health sciences
0302 clinical medicine
Endocrinology
Glucocorticoid receptor
Receptors, Glucocorticoid
Cell Line, Tumor
microRNA
medicine
Humans
RNA, Antisense
Child
Molecular Biology
Glucocorticoids
Cell Proliferation
Gene Expression Regulation, Leukemic
Lymphoblast
Cell Biology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
Cell culture
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Child, Preschool
Molecular Medicine
Female
Bone marrow
Glucocorticoid
Metabolism, Inborn Errors
medicine.drug
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 18791220
- Volume :
- 172
- Database :
- OpenAIRE
- Journal :
- The Journal of steroid biochemistry and molecular biology
- Accession number :
- edsair.doi.dedup.....14e48ac9f86fcb5c5a1e994b8e072fc7