TY  - EJOU
AU  - Wang, Zhiguo 
AU  - Fang, Zehui 
AU  - Lu, Runzhang 
AU  - Zhao, Hongli 
AU  - Gong, Tiejun 
AU  - Liu, Dong 
AU  - Hong, Luojia 
AU  - Ma, Jun 
AU  - Zhang, Mei 

TI  - MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia  Cells to Arsenic Trioxide
T2  - Oncology Research

PY  - 2019
VL  - 27
IS  - 9
SN  - 1555-3906

AB  - 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.
KW  - Acute myeloid leukemia (AML); Arsenic trioxide (ATO); miR-204; Apoptosis; BIRC6

DO  - 10.3727/096504019X15528367532612