SLC7A11在急性髓系白血病患者中的表达及抑制HL-60细胞增殖的机制

SLC7A11 expression in patients with acute myeloid leukemia and the mechanism of inhibiting HL-60 cells proliferation

目的:探讨SLC7A11 siRNA及Erastin对人急性髓系白血病(acute myeloid leukemia,AML)细胞株HL-60细胞活性的影响。方法:应用生物信息学方法分析癌症基因组图谱(The Cancer Genome Atlas,TCGA)中AML患者样本的数据,比较SLC7A11不同表达水平患者的预后。利用实时荧光定量聚合酶联反应(quantitative Real-time PCR,qRT-PCR)和蛋白质印记法(Western-blot)检测SLC7A11在AML患者和缺铁性贫血(iron deficiency anemia,IDA)患者中mRNA和蛋白的表达水平。培养人AML细胞株HL-60,用病毒介导的siRNA转染HL-60细胞,建立SLC7A11基因沉默的HL-60细胞株(siSLC7A11),用Erastin和DMSO分别处理HL-60细胞。利用qRT-PCR和Western-blot方法检测HL-60细胞和siSLC7A11细胞中SLC7A11的mRNA和蛋白的表达水平。利用CCK-8试剂盒检测细胞增殖情况。结果:SLC7A11的mRNA和蛋白表达水平在AML患者中明显高于IDA患者(P<0.05)。siSLC7A11细胞中SLC7A11的mRNA和蛋白表达水平明显低于对照组(P<0.05)。siSLC7A11细胞增殖率明显低于对照组(P<0.05)。结论:SLC7A11在AML患者中表达增加,通过siRNA或Erastin抑制SLC7A11能明显抑制人AML细胞株HL-60细胞增殖,SLC7A11基因可能成为治疗AML的新靶点。

Objective:To investigate the effect of SLC7A11 siRNA and Erastin on the cell viability of acute myeloid leukemia(AML)cells HL-60.Methods:The data of AML patients in The Cancer Genome Atlas(TCGA)were analyzed by bioinformatics method to compare the prognosis of patients with different expression levels of SLC7A11.The expression levels of SLC7A11 mRNA and protein in patients with AML and iron deficiency anemia(IDA)were detected by quantitative Real-time PCR(qRT-PCR)and Western-blot.HL-60 cells were cultured and transfected with virus mediated siRNA for SLC7A11 silencing(siSLC7A11).HL-60 cells were also treated with Erastin or DMSO.The mRNA and protein expression levels of SLC7A11 in HL-60 cells and siSLC7A11 cells were detected by qRT-PCR and Western-blot.Cell viability was detected by CCK-8 kit.Results:The mRNA and protein expression levels of SLC7A11 in AML patients were significantly higher than those in IDA patients(P<0.05).The mRNA and protein expression levels of SLC7A11 in siSLC7A11 cells were significantly lower than those in the control group(P<0.05).The proliferation rate of siSLC7A11 cells was significantly lower than theose in control group(P<0.05).Conclusion:The expression of SLC7A11 is increased in AML patients.Inhibition of SLC7A11 by siRNA or Erastin can significantly inhibit the proliferation of AML HL-60 cells.SLC7A11 gene may become a new target for the treatment of AML.