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MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide
- Source :
- Oncology Research
- Publication Year :
- 2019
- Publisher :
- Cognizant Communication Corporation, 2019.
-
Abstract
- Although arsenic trioxide (ATO) is a well-known antileukemic drug used for acute promyelocytic leukemia treatment, the development of ATO resistance is still a big challenge. We previously reported that microRNA-204 (miR-204) was involved in the regulation of acute myeloid leukemia (AML) cell apoptosis, but its role in chemoresistance is poorly understood. In the present study, we showed that miR-204 was significantly increased in AML cells after ATO treatment. Interestingly, the increased miR-204 level that was negatively correlated with ATO induced the decrease in cell viability and baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression. Overexpression of miR-204 potentiated ATO-induced AML cell growth inhibition and apoptosis. Furthermore, miR-204 directly targets to the 3′-UTR of BIRC6. Upregulation of miR-204 decreased BIRC6 luciferase activity and expression, which subsequently enhanced the expression of p53. Restoration of BIRC6 markedly reversed the effect of miR-204 on the regulation of AML cell sensitivity to ATO. Taken together, our study demonstrates that miR-204 decreases ATO chemoresistance in AML cells at least partially via promoting BIRC6/p53-mediated apoptosis. miR-204 represents a novel target of ATO, and upregulation of miR-204 may be a useful strategy to improve the efficacy of ATO in AML treatment.
- Subjects :
- 0301 basic medicine
Acute promyelocytic leukemia
Cancer Research
Myeloid
Apoptosis
Antineoplastic Agents
HL-60 Cells
Article
Inhibitor of Apoptosis Proteins
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Arsenic Trioxide
Arsenic trioxide (ATO)
Cell Line, Tumor
medicine
Acute myeloid leukemia (AML)
Humans
Arsenic trioxide
Chemistry
Cell growth
BIRC6
Myeloid leukemia
miR-204
General Medicine
medicine.disease
Up-Regulation
Leukemia
Leukemia, Myeloid, Acute
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Cancer research
Tumor Suppressor Protein p53
Subjects
Details
- Language :
- English
- ISSN :
- 15553906 and 09650407
- Volume :
- 27
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Oncology Research
- Accession number :
- edsair.doi.dedup.....0ae54565a034e88d5f1809594c653765