1. Department of Hemotology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, PR China
2. Baoying Hospital of traditional Chinese Medicine, Yangzhou, Jiangsu, 225800,China
3. Cancer Institute of Integrated traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde hospital of Zhejiang Province, Hangzhou, Zhejiang, 310012, China
4. Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, PR China
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.
Keywords: micoRNA-9, EIF5A2, drug resistance, acute myeloid leukemia (AML)