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

Zhiguo Wang*†1, Zehui Fang‡1, Runzhang Lu, Hongli Zhao, Tiejun Gong, Dong Liu, Luojia Hong, Jun Ma, Mei Zhang*

* Department of Hematology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi Province, P.R. China
† Department of Bone Marrow Transplantation, Harbin Hematological Cancer Institute, Harbin the First Hospital, Harbin Province, P.R. China
‡ Department of Endocrinology, the 4th Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, P.R. China

Oncology Research 2019, 27(9), 1035-1042.


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 repeatcontaining 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.


Cite This Article

Wang, Z., Fang, . Z., Lu, . R., Zhao, H., Gong, T. et al. (2019). MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide. Oncology Research, 27(9), 1035–1042.

This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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