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首页> 外文期刊>Biological chemistry >HDAC8 promotes daunorubicin resistance of human acute myeloid leukemia cells via regulation of IL-6 and IL-8
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HDAC8 promotes daunorubicin resistance of human acute myeloid leukemia cells via regulation of IL-6 and IL-8

机译:HDAC8通过调节IL-6和IL-8促进人急性髓性白血病细胞的Daunorubicin抗性

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摘要

The chemoresistance is one of the major challenges for acute myeloid leukemia (AML) treatment. We found that the expression of histone deacetylase 8 (HDAC8) was increased in daunorubicin (DNR) resistant AML cells, while targeted inhibition of HDAC8 by its specific siRNA or inhibitor can restore sensitivity of DNR treatment. Further, targeted inhibition of HDAC8 can suppress expression of interleukin 6 (IL-6) and IL-8. While recombinant IL-6 (rIL-6) and rIL-8 can reverse si-HDAC8-resored DNR sensitivity of AML cells. Mechanistical study revealed that HDAC8 increased the expression of p65, one of key components of NF-kappa B complex, to promote the expression of IL-6 and IL-8. It might be due to that HDAC8 can directly bind with the promoter of p65 to increase its transcription and expres-sion. Collectively, our data suggested that HDAC8 promotes DNR resistance of human AML cells via regulation of IL-6and IL-8.
机译:化学抑制是急性髓性白血病(AML)治疗的主要挑战之一。 我们发现,组蛋白脱乙酰酶8(HDAC8)的表达在Daunorubicin(DNR)抗性AML细胞中增加,同时通过其特定siRNA或抑制剂对HDAC8的靶向抑制可以恢复DNR处理的敏感性。 此外,靶向抑制HDAC8可以抑制白细胞介素6(IL-6)和IL-8的表达。 虽然重组IL-6(RIL-6)和RIL-8可以反转Si-HDAC8重组的AML细胞的DNR敏感性。 机械研究表明,HDAC8增加了P65的表达,NF-Kappa B复合物的关键组分之一,促进IL-6和IL-8的表达。 由于HDAC8可能与P65的启动子直接结合,以增加其转录和表达。 集体,我们的数据表明HDAC8通过IL-6和IL-8的调节促进人AML细胞的DNR抗性。

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  • 来源
    《Biological chemistry》 |2021年第4期|共8页
  • 作者单位

    Sun Yat Sen Univ Dept Hematol &

    Hematol Affiliated Hosp 3 600 Tianhe Ave Guangzhou 510630;

    Sun Yat Sen Univ Dept Hematol &

    Hematol Affiliated Hosp 3 600 Tianhe Ave Guangzhou 510630;

    Sun Yat Sen Univ Dept Hematol &

    Hematol Affiliated Hosp 3 600 Tianhe Ave Guangzhou 510630;

    Sun Yat Sen Univ Dept Hematol &

    Hematol Affiliated Hosp 3 600 Tianhe Ave Guangzhou 510630;

    Sun Yat Sen Univ Dept Hematol &

    Hematol Affiliated Hosp 3 600 Tianhe Ave Guangzhou 510630;

    Sun Yat Sen Univ Dept Hematol &

    Hematol Affiliated Hosp 3 600 Tianhe Ave Guangzhou 510630;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    AML; HDAC8; IL-6; IL-8; p65; resistance;

    机译:AML;HDAC8;IL-6;IL-8;P65;抗性;

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