Inhibition of the miR-143/145 cluster attenuated neutrophil differentiation of APL cells

Inhibition of the miR-143/145 cluster attenuated neutrophil differentiation of APL cells
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DOI:
10.1016/j.leukres.2011.10.006
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发表时间:
2012-02-01
期刊:
影响因子:
2.7
通讯作者:
Tschan, Mario P.
Tschan, Mario P.
中科院分区:
医学3区
文献类型:
--
作者:
Batliner, Jasmin;Buehrer, Emanuel;Tschan, Mario P.

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microrna可以影响造血细胞谱系的承诺,造血microrna的异常表达有助于AML病理。我们发现,与健康供者的中性粒细胞相比,miR-143和miR-145在原发性AML患者样本中的表达明显受到抑制。进一步分析显示,抑制miR-145表达后,APL细胞的中性粒细胞分化受损。最后,我们发现p73是APL细胞中性粒细胞分化过程中miR-143/145的转录调节因子。我们的数据表明,APL中miR-145的低水平,可能是由于p73转录因子的异常表达,导致了这种疾病的分化受阻。(C) 2011 Elsevier Ltd.版权所有。
MicroRNAs can influence hematopoietic cell lineage commitment and aberrant expression of hematopoietic miRNAs contributes to AML pathology. We found that miR-143 and miR-145 expression is significantly repressed in primary AML patient samples as compared to neutrophils of healthy donors. Further analysis revealed impaired neutrophil differentiation of APL cells upon inhibition of miR-145 expression. Lastly, we identified p73 as transcriptional regulator of miR-143/145 during neutrophil differentiation of APL cells. Our data suggest that low miR-145 levels in APL, possibly due to aberrant expression of p73 transcription factors, contribute to the differentiation block seen in this disease. (C) 2011 Elsevier Ltd. All rights reserved.