MiR-181a Promotes Proliferation of Human Acute Myeloid Leukemia Cells by Targeting ATM.

Jia-Ye HUA; Ying FENG; Ying PANG; Xu-Hong ZHOU; Bing XU; Mu-Xia YAN

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MiR-181a Promotes Proliferation of Human Acute Myeloid Leukemia Cells by Targeting ATM.

Author: Jia-Ye HUA ^{1
,

2} ; Ying FENG ³ ; Ying PANG ³ ; Xu-Hong ZHOU ³ ; Bing XU ⁴ ; Mu-Xia YAN ⁵
Author Information

1. Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China. E-mail: jy1016aa@
2. com.
3. Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China.
4. Department of Hematology, Nanfang Hospital, Southern Medical University, Guanghzou 510515, Guangdong Province, China.
5. Hematology Laboratory, Guangzhou Women and Children Medical Center, Guangzhou 510623, Guangdong Province, China.
Publication Type:Journal Article
MeSH: Ataxia Telangiectasia Mutated Proteins; metabolism; Cell Proliferation; Down-Regulation; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; metabolism; pathology; MicroRNAs; genetics; metabolism; Transfection
From: Journal of Experimental Hematology 2016;24(2):347-351
CountryChina
Language:Chinese
Abstract:
OBJECTIVETo investigate miR-181a function and regulation mechanism by identifying miR-181a target genes in acute myeloid leukemia (AML).
METHODSThe HL-60 cells of human AML was transfected by small molecular analog miR-181a, the cell proliferation was detected by CCK-8 method after electroporation in HL-60 cell lines. Target genes of miR-181a were predicted and analyzed by the bioinformatics software and database. Target genes were confirmed by HL-60 cell line and the patient leukemia cells.
RESULTSOverexpressed miR-181a in HL-60 cell line significantly enhanced cell proliferation compared with that in control (P < 0.05). Dual luciferase reporter gene assay showed that miR-181a significantly suppressed the reporter gene activity containing ATM 3'-UTR by about 56.8% (P < 0.05), but it didn't suppress the reporter gene activity containing 3'-UTR ATM mutation. Western blot showed that miR-181a significantly downregulated the expression of ATM in human leukemia cells. It is also found that miR-181a was significantly increased in AML, which showed a negative correlation with ATM expression.
CONCLUSIONmiR-181a promotes cell proliferation in AML by regulating the tumor suppressor ATM, thus it plays the role as oncogene in pathogenesis of AML.