MicroRNA-145 promotes the apoptosis of leukemic stem cells and enhances drug-resistant K562/ADM cell sensitivity to adriamycin via the regulation of ABCE1

Abstract

Leukemia is a type of cancer which originates in blood-forming tissues. MicroRNAs (miRNAs or miRs) have been shown to be involved leukemogenesis. In the present study, following the gain- and loss-function of miR-145 and ATP-binding cassette sub-family E member 1 (ABCE1) in K562 cells and K562 adriamycin-resistant cells (K562/AdM cells), the levels of multidrug resistance protein 1 (MRP1) and P-glycoprotein (P-gp) were measured. The viability of the K562 cells and K562/AdM cells treated with various concentrations of ADM, and cell sensitivity to AdM were measured. The apoptosis of stem cells was detected. K562/ADM cells were transfected with miR-145 mimic or with miR-145 mimic together with ABCE1 overexpression plasmid to examine the effects of ABcE1 on the sensitivity of K562/AdM cells to AdM. The association between miR-145 and ABCE1/MRP1 was then verified. The dose- and time-dependent effects of ADM on the K562 cells and K562/ADM cells were examined. The K562/ADM cells exhibited a greater resistance to AdM, higher levels of MRP1 and P-gp, and a lower miR-145 expression. The K562/AdM cells and stem cells in which miR-145 was overexpressed exhibited a suppressed cell proliferation, decreased MRP1 and P-gp levels, and an increased apoptotic rate. However, K562 cells with a low expression of miR-145 exhibited an increased cell proliferation, increased levels of MRP1 and P-gp, and a suppressed apoptotic rate. compared with the overexpression of miR-145, the combination of miR-145 and ABCE1 decreased the sensitivity of drug-resistant K562/AdDM cells to AdM. The above-mentioned effects of miR-145 were achieved by targeting ABCE1. Taken together, the findings of the present study demonstrate that the overexpression of miR-145 promotes leukemic stem cell apoptosis and enhances the sensitivity of K562/ADM cells to AdM by inhibiting ABCE1.