MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide

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.

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

“…MiR-15a-5p induces resistance, whereas miR-9 enhances sensitivity of AML cells to daunorubicin through the abrogation of autophagy and by targeting the EIF5A2/MCL-1 axis, respectively [ 161 , 162 ]. MiR-217 enhances chemosensitivity of AML cells to doxorubicin by targeting KRAS [ 163 ], while miR-204 potentiates the sensitivity of acute promyelocytic leukemia (APL) cells to arsenic trioxide (ATO) [ 164 ]. MiR-29a and miR-100 were identified as significant predictors of chemotherapy response in pediatric AML [ 165 ].…”

One Omics Approach Does Not Rule Them All: The Metabolome and the Epigenome Join Forces in Haematological Malignancies

“…Reduced expression of miR-204 is observed in AML, where its overexpression leads to cell apoptosis by targeting BIRC6 [ 193 ]. Moreover, expression of miR-204 potentiates sensitivity of AML cells to arsenic trioxide [ 194 ]. Overexpression of miR-125a/b in AML and MDS also exerts antioncogenic and prodifferentiation effects by modulating the NF-κB signalling pathway [ 195 , 196 , 197 ].…”

Expression and Clinical Value of Eukaryotic Translation Elongation Factor 1A1 (EEF1A1) in Diffuse Large B Cell Lymphoma

“…The cell viability was detected by cell counting kit-8 (CCK-8) assay as we described previously. 25 Briefly, stable transfected cells and control cells were seeded into a 96-well plate at a density of 2×10 3 cells/well. After cultured at 37 °C with 5% CO 2 for designated time points (8, 24, 48, 72, and 96 hours).…”