BMB Reports 2018; 51(9): 444-449  https://doi.org/10.5483/BMBRep.2018.51.9.036
MiR-204 acts as a potential therapeutic target in acute myeloid leukemia by increasing BIRC6-mediated apoptosis
Zhiguo Wang1,2,#,*, Hong Luo3,#, Zehui Fang4, Yanling Fan2, Xiaojuan Liu2, Yujing Zhang4, Shuping Rui2, Yafeng Chen2, Luojia Hong4, Jincheng Gao4 & Mei Zhang1,*
1Department of Hematology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shanxi Province, 2Department of Bone Marrow Transplantation, Harbin Hematological Cancer Institute, Harbin the First Hospital, Harbin 150010, 3Department of Hematology, the First Hospital of Qiqihar, Qiqihar 150001, 4Department of Endocrinology, the 4th Affiliated Hospital of Harbin Medical University, Harbin 161000, Heilongjiang Province, People’s Republic of China
Correspondence to: Mei Zhang, Tel: +86-029-85323112; Fax: +86-029-85323112; E-mail: zhangmeimed@yeah.net; Zhiguo Wang, Tel: +86-029-85323112; Fax: +86-029-85323112; E-mail: wangzhiguo91006@163.com
#These authors contributed equally to this work.
Received: February 15, 2018; Revised: March 13, 2018; Accepted: April 23, 2018; Published online: September 30, 2018.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

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Abstract
Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204. Our results showed that miR-204 expression was significantly downregulated in AML tissues and cell lines. In addition, overexpression of miR-204 induced growth inhibition and apoptosis in AML cells, including AML5, HL-60, Kasumi-1 and U937 cells. Cell cycle analysis further confirmed an augmentation in theapoptotic subG1 population by miR-204 overexpression. Mechanistically, baculoviral inhibition of apoptosis protein repeat containing 6 (BIRC6) was identified as a direct target of miR-204. Enforcing miR-204 expression increased the luciferase activity and expression of BIRC6, as well as p53 and Bax expression. Moreover, restoration of BIRC6 reversed the pro-apoptotic effects of miR-204 overexpression in AML cells. Taken together, this study demonstrates that miR-204 causes AML cell apoptosis by targeting BIRC6, suggesting miR-204 may play an anti-carcinogenic role in AML and function as a novel biomarker and therapeutic target for the treatment of this disease.
Keywords: Acute myeloid leukemia, Apoptosis, BIRC6, Cell cycle, microRNA-204


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