MiR-181a Promotes Proliferation of Human Acute Myeloid Leukemia Cells by Targeting ATM / 中国实验血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate miR-181a function and regulation mechanism by identifying miR-181a target genes in acute myeloid leukemia (AML).</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>Overexpressed 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.</p><p><b>CONCLUSION</b>miR-181a promotes cell proliferation in AML by regulating the tumor suppressor ATM, thus it plays the role as oncogene in pathogenesis of AML.</p>