We investigated the role of leukemia stem cells in chemoresistance and recurrence of acute myeloid leukemia. Total RNA was isolated from cells or tissues using TRIzol reagent. Cell viability was assessed with the tetrazolium assay. MicroRNA‐34a (miR‐34a), which acts on cell death regulation pathways, was noticeably downregulated in non‐M3 acute myeloid leukemia stem cells compared with normal hematopoietic stem cells. Furthermore, inhibition of miR‐34a‐mediated suppression in leukemia stem cells was associated with poor clinical outcomes and impaired treatment efficacy in acute myeloid leukemia. Transfection with a miR‐34a mimic triggered leukemia stem cell death and prevented leukemia. Bioinformatics analysis and a dual‐luciferase reporter assay showed that miR‐34a targeted the 3′‐untranslated region of histone deacetylase 2, and the reinforced expression of miR‐34a remarkably stimulated the expression of histone deacetylase 2 in leukemia stem cells. Ectopic miR‐34a expression triggered death of leukemia stem cells via pathways involving the Janus kinase 1‐signal transducer and activator of transcription 2‐p53 axis. Targeting leukemia stem cells to trigger cell death through upregulation of miR‐34a expression could be used to diagnose and treat acute myeloid leukemia.

中文翻译：

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MicroRNA-34a 介导的急性髓系白血病干细胞死亡通过组蛋白去乙酰化酶 2 靶向诱导凋亡和外泌体脱落抑制

我们研究了白血病干细胞在急性髓性白血病的化学抗性和复发中的作用。使用 TRIzol 试剂从细胞或组织中分离总 RNA。用四唑鎓分析评估细胞活力。与正常造血干细胞相比，作用于细胞死亡调节途径的 MicroRNA-34a (miR-34a) 在非 M3 急性髓系白血病干细胞中显着下调。此外，抑制 miR-34a 介导的白血病干细胞抑制与临床结果不佳和急性髓性白血病治疗效果受损有关。用 miR-34a 模拟物转染引发白血病干细胞死亡并预防白血病。生物信息学分析和双荧光素酶报告基因检测表明 miR-34a 靶向组蛋白去乙酰化酶 2 的 3' 非翻译区，miR-34a 的增强表达显着刺激了白血病干细胞中组蛋白去乙酰化酶 2 的表达。异位 miR-34a 表达通过涉及 Janus 激酶 1 信号转导和转录激活因子 2-p53 轴的通路引发白血病干细胞的死亡。靶向白血病干细胞通过上调 miR-34a 表达触发细胞死亡可用于诊断和治疗急性髓系白血病。