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/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.

RETRACTED: MiR-145 modulation of TGF-β pathway attenuates EMT inhibition of Wilms’Tumor cell proliferation, invasion and migration

“…MicroRNAs (miRNAs) are small,endogenous,non-coding RNA molecules that play pivotal roles in numerous biological processes including developmental timing, cell differentiation, embryogenesis, metabolism, organogenesis, apoptosis, and tumorigenesis [3,4] . Research has demonstrated that miRNA downregulation is prevalent in various cancers and is linked to cancer development,metastasis,and treatment response [5] . a relatively new discovery in the miRNA category,has been identi ed in WT through clinical data and specimen analysis.Increasing miR-145 levels have been shown to suppress the proliferation and migration of WT SK-NEP-1 cells, suggesting its role as a tumor suppressor gene [6] .…”

Influence of Human Bone Marrow Mesenchymal Stem Cells Secretome from Acute Myeloid Leukemia Patients on the Proliferation and Death of K562 and K562-Lucena Leukemia Cell Lineages

“…Wu at al. (2021) described that both IL-6 and IL-8 levels are increased in resistant acute myeloid leukemia cells [57].…”

“…Thus, IL-8 could promote proliferation and resistance in acute myeloid leukemia cells, while IL-6 predicts survival rate and regulates the drug resistance in these cells [57].…”

Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia

“…For example, Let-7, miR-23A, and miR-223 have been reported to act as tumor suppressors in CML ( 29 – 31 ). miR-145 and miR-181 promote apoptosis of leukemia stem cells through regulation of ABCE1 and MCL-1 respectively ( 32 , 33 ), and miR-424 inhibits BCR-ABL activity ( 34 ). Comparatively, the miR-126 is associated with leukemia stem cell maintenance ( 35 ), miR-17 promotes leukemia proliferation by targeting p21 ( 36 ), over-expression of miR-106 and miR-222 will promote CML proliferation ( 37 ), and miR-92a-1-5p inhibits TKI-induced necroptosis by targeting MLKL ( 38 ).…”