Institute of Hematology, Medical College, Jinan University, Guangzhou 510632, China.
Institute of Hematology, Medical College, Jinan University, Guangzhou 510632, China ; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, China.
Exp Hematol Oncol. 2014 Jul 1;3:17. doi: 10.1186/2162-3619-3-17. eCollection 2014.
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.
miR-29 家族已被证明在多种癌症中作为重要的肿瘤抑制因子，以及在适应性免疫系统中作为调节剂发挥作用。然而，关于其在白血病发生中的作用知之甚少。本研究旨在分析 miR-29a/29b 及其靶基因 Mcl-1（髓细胞白血病序列 1）和 Bcl-2（B 细胞淋巴瘤 2）在髓性白血病中的表达模式。
采用实时定量 PCR 检测 10 例初诊未治疗的急性髓系白血病（AML）和 14 例初诊未治疗的慢性髓系白血病慢性期（CML）患者外周血单个核细胞（PBMCs）中基因的表达水平，并以 14 例健康个体（HI）作为对照。分析不同基因相对表达水平之间的相关性。
与 HI 组相比，AML 和 CML 患者 PBMCs 中 miR-29a/29b 的表达水平显著降低，而两个潜在靶基因 Bcl-2 和 Mcl-1 的表达水平升高。此外，AML 患者 miR-29a 的表达明显低于 CML 患者。此外，还发现 miR-29a/29b 与其靶基因之间存在负相关。然而，在 38 例研究对象中，miR-29a 的相对表达水平与 miR-29b 或 Bcl-2 和 Mcl-1 之间呈正相关。
下调的 miR-29a 和 miR-29b，以及伴随的上调的 Bcl-2 和 Mcl-1 是髓性白血病的共同特征。这些数据进一步支持 miR-29a/29b 失调在髓性白血病发生中的作用，以及未来调节 miR-29a/29b 表达治疗髓性白血病的治疗潜力。
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