Altered expression pattern of miR-29a, miR-29b and the target genes in myeloid leukemia.

Altered expression pattern of miR-29a, miR-29b and the target genes in myeloid leukemia.
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DOI:
10.1186/2162-3619-3-17
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发表时间:
2014
影响因子:
10.9
通讯作者:
Li Y
Li Y
中科院分区:
医学2区
文献类型:
--
作者:
Xu L;Xu Y;Jing Z;Wang X;Zha X;Zeng C;Chen S;Yang L;Luo G;Li B;Li Y

文献摘要

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MiR-29家族已被证明在多种癌症中发挥重要的肿瘤抑制作用,并在适应性免疫系统中发挥调节作用。人们对它们在白血病发生中的作用知之甚少。本研究的目的是分析miR-29a/29b及其靶基因Mcl-1(髓系细胞白血病序列1)和B细胞淋巴瘤2(Bcl-2)在髓系白血病中的表达模式。采用实时定量聚合酶链式反应技术检测10例初诊、初治急性髓系白血病(AML)和14例初诊、初治慢性粒细胞白血病(CML)慢性期患者外周血单个核细胞(PBMC)基因表达水平,并以14例健康人(HI)作对照。分析了不同基因的相对表达水平之间的相关性。与HI组相比,AML和CML患者PBMC中miR-29a/29b的表达显著降低,而两个潜在靶基因Bcl2和Mcl-1的表达水平明显升高。此外,miR-29a在AML中的表达明显低于CML。此外,还发现miR-29a/29b与其靶基因呈负相关。而在38例研究对象中,miR-29a与miR-29b或Bcl2与Mcl-1的相对表达水平呈正相关。髓系白血病的共同特征是miR-29a和miR-29b表达下调,同时伴有Bcl2和Mcl-1表达上调。这些数据进一步支持了miR-29a/29b异常在髓系白血病发生中的作用,以及未来调节miR-29a/29b表达对髓系白血病的治疗前景。
The miR-29 family have been demonstrated acting as vital tumor suppressor in multiple cancers as well as regulators in the adaptive immune system. Little is known about their role in leukemogenesis. The purpose of this study is to analyze the expression pattern of miR-29a/29b and its target genes Mcl-1 (myeloid cell leukemia sequence 1) and B-cell lymphoma 2 (Bcl-2) in myeloid leukemia. Quantitative real-time PCR was used for detecting genes expression level in peripheral blood mononuclear cells (PBMCs) from 10 cases with newly diagnosed, untreated acute myeloid leukemia (AML) and 14 cases with newly diagnosed, untreated chronic myeloid leukemia (CML) in chronic phase, and 14 healthy individual (HI) served as controls. Correlation between the relative expression levels of different genes have been analyzed. Significant lower expression of miR-29a/29b and higher expression level of two potential target genes Bcl-2 and Mcl-1 were found in PBMCs from AML and CML patients compared with HI group. In addtion, miR-29a expression in AML was significantly lower than that in CML. Moreover, negative correlation between miR-29a/29b and its target genes have been found. While, positive correlation between relative expression level of miR-29a and miR-29b or Bcl-2 and Mcl-1 were presented in the total 38 research objects. Down-regulated miR-29a and miR-29b, and accompanying up-regulated Bcl-2 and Mcl-1 are the common feature in myeloid leukemias. These data further support the role for miR-29a/29b dysregulation in myeloid leukemogenesis and the therapeutic promise of regulating miR-29a/29b expression for myeloid leukemia in the future.