miR-331-3p is involved in glucocorticoid resistance reversion by rapamycin through suppression of the MAPK signaling pathway
0301 basic medicine
Apoptosis
03 medical and health sciences
Glucocorticoids; miRNA; Pharmacoepigenetics; Rapamycin
Glucocorticoid
Biomarkers, Tumor
Tumor Cells, Cultured
Humans
Rapamycin
Glucocorticoids
miRNA
Cell Proliferation
Sirolimus
0303 health sciences
Antibiotics, Antineoplastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
3. Good health
Pharmacoepigenetic
Gene Expression Regulation, Neoplastic
MicroRNAs
Pharmacoepigenetics
Drug Resistance, Neoplasm
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Original Article
Mitogen-Activated Protein Kinases
DOI:
10.1007/s00280-020-04122-z
Publication Date:
2020-08-10T11:02:50Z
AUTHORS (14)
ABSTRACT
Abstract Glucocorticoids (GCs) are commonly used as therapeutic agents for immune-mediated diseases and leukemia. However, considerable inter-individual differences in efficacy have been reported. Several reports indicate that the inhibitor of mTOR rapamycin can reverse GC resistance, but molecular mechanism involved this synergistic effect has not fully defined. In context, we explored differential miRNA expression a GC-resistant CCRF-CEM cell line after treatment with alone or co-treatment methylprednisolone (MP). The analysis identified 70, 99 96 miRNAs were differentially expressed MP, their combination compared to non-treated controls, respectively. Two pathways exclusively altered result co-treatment: MAPK ErbB pathways. We validated only upregulated specifically by associated signaling, miR-331-3p. Looking miR-331-3p targets, MAP2K7, an essential component JNK/MAPK pathway, was identified. Interestingly, MAP2K7 downregulated during co-treatment, causing decrease terms JNK activity. mimic-transfected cells led significant levels promoted reversion resistance vitro. also GC-resistance patient leukemia taken at diagnosis. MP restores effectiveness through regulation different miRNAs, suggesting important role these pharmacoepigenetic factors response.
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CITATIONS (10)
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