Work

miR-9 Enhances the Chemosensitivity of AML Cells to Daunorubicin by Targeting the EIF5A2/MCL-1 Axis

Year: 2019

Type: article

Abstract: 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.

Source: International Journal of Biological Sciences

DOI: 10.7150/ijbs.29775