Decreased expression of microRNA-214 contributes to imatinib mesylate resistance of chronic myeloid leukemia patients by upregulating ABCB1 gene expression.
The aim of the present study was to determine the expression of adenosine triphosphate binding cassette subfamily B member 1 (ABCB1) gene and its protein P-glycoprotein (PGP) in bone marrow mononuclear cells from chronic myeloid leukemia (CML) patients with imatinib mesylate (IM) resistance, or IM-resistant CML K562 cells. In addition, the molecular mechanism of action of microRNA (miR)-214 on ABCB1 in IM resistance was investigated. A total of 26 CML patients with IM resistance were included in the present study. In addition, 31 CML patients who did not have IM resistance were included as the control group. Bone marrow was collected from all subjects. The K562R cell line, which is a K562 cell line with IM resistance, was used for cellular studies. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression of ABCB1 mRNA and miR-214 in cells. Western blotting was employed to determine the expression of PGP. Dual luciferase reporter assay was carried out to identify interactions between ABCB1 mRNA and miR-214. MTT assay was used to determine the survival rate of cells. ABCB1 mRNA and PGP expression was upregulated in bone marrow mononuclear cells from CML patients with IM resistance. K562R cells had higher ABCB1 and PGP expression than K562 cells, potentially due to their different sensitivity to IM. Expression miR-214 was decreased in bone marrow mononuclear cells from patients with IM resistance and K562R cells. Notably, miR-214 was able to bind with the 3'-untranslated region, seed region of ABCB1 mRNA to regulate its expression. In addition, elevated expression of miR-214 restored IM sensitivity to K562R cells potentially by affecting ABCB1 expression. The present study demonstrated that upregulated expression of ABCB1 mRNA and PGP in bone marrow mononuclear cells from CML patients with IM resistance may be associated with the downregulation of miR-214. In addition, miR-214 may participate in the IM resistance of CML patients by regulating ABCB1 expression.
['Jin|Jing|J|', 'Yao|Jia|J|', 'Yue|Fang|F|', 'Jin|Zhaoying|Z|', 'Li|Dan|D|', 'Wang|Shan|S|']
microRNA-214 imatinib mesylate P-glycoprotein adenosine triphosphate binding cassette subfamily B member 1 gene drug resistance