Open AccessEstablishment and molecular characterization of decitabine‐resistant K562 cells
Author(s) -
Wen XiangMei,
Zhang TingJuan,
Ma JiChun,
Zhou JingDong,
Xu ZiJun,
Zhu XiaoWen,
Yuan Qian,
Ji RunBi,
Chen Qin,
Deng ZhaoQun,
Lin Jiang,
Qian Jun
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14221
Subject(s) - decitabine , k562 cells , ectopic expression , cell culture , myeloid leukemia , cancer research , hypomethylating agent , leukemia , downregulation and upregulation , apoptosis , biology , chemistry , medicine , gene expression , gene , immunology , dna methylation , biochemistry , genetics
Abstract The clinical activity of decitabine (5‐aza‐2‐deoxycytidine, DAC), a hypomethylating agent, has been demonstrated in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients. However, secondary resistance to this agent often occurs during treatment and leads to treatment failure. It is important to clarify the mechanisms underlying the resistance for improving the efficacy. In this study, by gradually increasing concentration after a continuous induction of DAC, we established the DAC‐resistant K562 cell line (K562/DAC) from its parental cell line K562. The proliferation and survival rate of K562/DAC was significantly increased, whereas the apoptosis rate was remarkably decreased than that of K562 after DAC treatment. In K562/DAC, a total of 108 genes were upregulated and 118 genes were downregulated by RNA‐Seq. In addition, we also observed aberrant expression of DDX43/H19/miR‐186 axis (increased DDX43 / H19 and decreased miR‐186 ) in K562/DAC cells. Ectopic expression of DDX43 in parental K562 cells rendered cells resistant to the DAC. Taken together, we successfully established DAC‐resistant K562 cell line which can serve as a good model for investigating DAC resistance mechanisms, and DDX43/H19/miR‐186 may be involved in DAC resistance in K562.