miR-9 Enhances the Chemosensitivity of AML Cells to Daunorubicin by Targeting the EIF5A2/MCL-1 Axis.
Daunorubicin (Dnr) is at the forefront of acute myeloid leukemia (AML) therapy, but drug resistance poses a major threat to treatment success. MicroRNA (miR)-9 has been shown to have a pivotal role in AML development. However, little is known about the role of miR-9 in Dnr resistance in AML. We explored the potential role of miR-9 in Dnr resistance in AML cells and its mechanism of action. AML cell lines with high half-maximal inhibitory concentration to Dnr in vivo had significantly low miR-9 expression. miR-9 overexpresssion sensitized AML cells to Dnr, inhibited cell proliferation, and enhanced the ability of Dnr to induce apoptosis; miR-9 knockdown had the opposite effects. Mechanistic studies demonstrated that eukaryotic translation initiation factor 5A-2 (EIF5A2) was a putative target of miR-9, which was inversely correlated with the expression and role of miR-9 in AML cells. miR-9 improved the anti-tumor effects of Dnr by inhibiting myeloid cell leukemia-1 (MCL-1) expression, which was dependent on downregulation of EIF5A2 expression. These results suggest that miR-9 has an essential role in Dnr resistance in AML cells through inhibition of the EIF5A2/MCL-1 axis in AML cells. Our data highlight the potential application of miR-9 in chemotherapy for AML patients.
['Liu|Yanhui|Y|', 'Lei|Pingchong|P|', 'Qiao|Hong|H|', 'Sun|Kai|K|', 'Lu|Xiling|X|', 'Bao|Fengchang|F|', 'Yu|Runhong|R|', 'Lian|Cheng|C|', 'Li|Yao|Y|', 'Chen|Wei|W|', 'Xue|Fei|F|']
D017209:Apoptosis D015153:Blotting, Western D045744:Cell Line, Tumor D049109:Cell Proliferation D018922:HL-60 Cells D006801:Humans D015470:Leukemia, Myeloid, Acute D035683:MicroRNAs D064549:Myeloid Cell Leukemia Sequence 1 Protein D010448:Peptide Initiation Factors D016601:RNA-Binding Proteins D060888:Real-Time Polymerase Chain Reaction
EIF5A2 acute myeloid leukemia (AML) drug resistance micoRNA-9