Roles of MicroRNA-223 in regulating Chemotherapeutic drug resistance in KG-1a Leukemic Stem Cell line

Abstract

Drug resistance is the major cause of chemotherapeutics failure, which contributes to the short-term survival of patients with acute myeloblastic leukemia (AML). Although the precise mechanisms of resistance are poorly understood, but they may relate to the presence of leukemic stem cells (LSCs). MicroRNA-223 (miR-223) dysregulation has been reported in both upregulation and downregulation in several cancers, including AML. However, no studies have been conducted to investigate the significance of miR-223 in LSCs, particularly those involved in the drug resistance mechanism. To elucidate the role of miR-223 in regulating chemotherapeutic drug resistance in leukemic stem cell line, a combination of molecular biology techniques and bioinformatics was used to study the mechanisms. The viability of KG-1 and KG-1a cells treated with various concentrations of doxorubicin (DOX) was examined to determine DOX sensitivity in both cell lines. KG-1a cells were transfected with miR-223 mimic to examine the effects of miR-223 on the DOX sensitivity of KG-1a cells. The association between miR-223 and protein kinase C epsilon (PKCε), a target of miR-223, was then verified. The results showed that the KG-1a cells exhibited a greater resistance to DOX, higher levels of PKCε, and a lower miR-223 expression level. The transfection of miR-223 in KG-1a led to downregulation of PKCε protein. The result of luciferase assay also verified that miR-223 could targeted and silenced the expression of PKCε. However, miR-223 overexpression could not restore DOX sensitivity in KG-1a cells. Overall, the findings of the present study demonstrated that miR-223 could target and silence the expression of PKCε in KG-1a cells, but the drug resistance event in KG-1a cells may not associate with the downregulation of miR-223. Further investigations still required to support the mechanisms illustrating the roles of miR-223 or PKCε in the drug resistance of LSCs.