MicroRNA‐33b regulates sensitivity to daunorubicin in acute myelocytic leukemia by regulating eukaryotic translation initiation factor 5A‐2

Abstract

In this study, we aimed to study the effect of miR‐33b in regulating sensitivity to daunorubicin (DNR) in acute myelocytic leukemia (AML). We used quantitative real‐time polymerase chain reaction and Cell Counting Kit‐8 assay to detect the level of miR‐33b and cell viability. Cell apoptosis and the expression of eIF5A‐2 and MCL‐1 protein were detected by flow cytometry analysis and Western Blot analysis, respectively. MiR‐33b mimic increased sensitivity of AML cells against DNR, while miR‐33b inhibitor had the opposite effect. Furthermore, the results showed that the eIF5A‐2 gene was a direct target of miR‐33b, and miR‐33b regulated eIF5A‐2 mRNA and protein expression. Silencing of eIF5A‐2 by RNA interference increased the sensitivity of AML cells against DNR. We also found that MCL‐1 contributed to the regulation of DNR sensitivity, which was dependent on downregulation of eIF5A‐2. Finally, knockdown of eIF5A‐2 eliminated the effects of miRNA‐33b mimic or inhibitor on DNR sensitivity. These findings indicate that miR‐33b maybe as a new therapeutic target in AML cells.

Recent insights into eukaryotic translation initiation factors 5A1 and 5A2 and their roles in human health and disease

“…MiR-30b, miR-125b, miR-203, miR-588, miR-221-3p, and miR-599 were proven to regulate the expression of EIF5A2 by directly targeting the 3′-UTR of EIF5A2 mRNA [28][29][30][31][32][33]. Also, the eIF5A2 protein was regulated by miR-33b, miR-383, and miR-9, but how these miRNAs regulated eIF5A2 protein would need to be further studied [34][35][36].…”