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Open Access MicroRNA-204 potentiates the sensitivity of acute myeloid leukemia cells to arsenic trioxide

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Although arsenic trioxide (ATO) is a well-known anti-leukemic 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 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.
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Keywords: BIRC6 ; acute myeloid leukemia; apoptosis; arsenic trioxide; miR-204

Affiliations: 1: Department of Hematology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shanxi Province, People’s Republic of China 2: Department of Bone Marrow Transplantation, Harbin Hematological Cancer Institute, Harbin the First Hospital, 150010, Harbin Province, People’s Republic of China 3: Department of Endocrinology, the 4th Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, People’s Republic of China

Appeared or available online: April 8, 2019

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