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

Wuxiao,Zhijun; Wang,Hua; Su,Qunhao; Zhou,Haiyan; Hu,Min; Tao,Shi; Xu,Lu; Chen,Yu; Hao,Xinbao

doi:10.3892/ijmm.2020.4675

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

Authors:
- Zhijun Wuxiao
- Hua Wang
- Qunhao Su
- Haiyan Zhou
- Min Hu
- Shi Tao
- Lu Xu
- Yu Chen
- Xinbao Hao
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Affiliations: Department of Hematology, Lymphoma and Myeloma Center, HMC Cancer Institute, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China, Department of Hematological Oncology, Sun Yat‑sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China
Published online on: July 15, 2020 https://doi.org/10.3892/ijmm.2020.4675
Pages: 1289-1300
Copyright: © Wuxiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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/ADM 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.

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