Isken Fabienne, Steffen Björn, Merk Sylvia, Dugas Martin, Markus Birgit, Tidow Nicola, Zühlsdorf Michael, Illmer Thomas, Thiede Christian, Berdel Wolfgang E, Serve Hubert, Müller-Tidow Carsten
Department of Medicine A, Haematology and Oncology, University of Münster, Münster, Germany.
Br J Haematol. 2008 Jan;140(2):153-61. doi: 10.1111/j.1365-2141.2007.06915.x.
MicroRNAs (miRNAs) play an important role in cellular differentiation and cancer pathogenesis. This study analysed the expression of 154 human miRNAs in acute myeloid leukaemia (AML) and control samples using a stem-loop real-time reverse transcription polymerase chain reaction approach. Global patterns of miRNA expression in AML, normal bone marrow (NBM) and CD34(+) progenitor cells allowed correct class predictions similar to whole genome microarray expression analyses that were performed at the same time. At single miRNA species level, MIRN23B was repressed in AML specimens compared to NBM and purified CD34(+) haematopoietic progenitor cells. In contrast, the MIRN221/MIRN222 cluster and MIRN34A were expressed at significantly higher levels in AML blasts. Patients with high MIRN221/MIRN222 expression showed low levels of KIT RNA and protein expression but the correlation between kit protein and KIT mRNA was significantly stronger than the correlation of either one with MIRN221/MIRN222. A global analysis between miRNA expression levels and mRNA expression of predicted target genes revealed only weak associations in the majority of miRNA species. Nonetheless, the presence of two or more miRNA binding sites within the mRNA was usually associated with a decrease in mRNA levels. Taken together, these findings provide evidence that specific miRNA expression patterns exist in AML.
微小RNA（miRNA）在细胞分化和癌症发病机制中发挥着重要作用。本研究采用茎环实时逆转录聚合酶链反应方法分析了154种人类miRNA在急性髓系白血病（AML）和对照样本中的表达情况。AML、正常骨髓（NBM）和CD34（+）祖细胞中miRNA表达的整体模式能够实现正确的类别预测，类似于同时进行的全基因组微阵列表达分析。在单个miRNA种类水平上，与NBM和纯化的CD34（+）造血祖细胞相比，MIRN23B在AML标本中表达受到抑制。相反，MIRN221/MIRN222簇和MIRN34A在AML原始细胞中的表达水平显著更高。MIRN221/MIRN222高表达的患者显示KIT RNA和蛋白表达水平较低，但KIT蛋白与KIT mRNA之间的相关性明显强于它们与MIRN221/MIRN222中任何一个的相关性。miRNA表达水平与预测靶基因mRNA表达之间的全局分析显示，在大多数miRNA种类中只有微弱的关联。尽管如此，mRNA内存在两个或更多miRNA结合位点通常与mRNA水平降低相关。综上所述，这些发现提供了证据表明AML中存在特定的miRNA表达模式。
