Coordinated expression of microRNA-155 and predicted target genes in diffuse large B-cell lymphoma
Coordinated expression of microRNA-155 and predicted target genes in diffuse large B-cell lymphoma
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DOI：
10.1016/j.cancergencyto.2007.10.008
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发表时间：
2008-02-01
影响因子：
--
通讯作者：
Aguiar, Ricardo C. T.
中科院分区：
文献类型：
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作者：
Rai, Deepak;Karanti, Shailaja;Aguiar, Ricardo C. T.
微小RNA（miRNAs）通过与靶转录物的3 'UTR配对诱导RNA切割或翻译抑制来减弱基因表达。microRNA-155（miR-155）的过度表达，无论是在初级（BIC基因）或成熟的转录水平，最近被描述在弥漫性大B细胞淋巴瘤（DLBCL）。然而，这些研究在规模上受到限制，并且没有试图将miR-155表达与推定的靶基因的表达联系起来。为了开始解决这些问题，我们检查了22个充分表征的DLBCL细胞系的集合。miR-155在这些细胞系中的表达是异质的，并且与NF-κ B活性相关。我们发现，原代miR-155转录物的表达可靠地反映了功能性成熟miR-155的表达。由于许多基因阵列平台包括主要miR-155序列的探针组，这些发现使我们能够在miR-155水平的背景下自信地检查主要DLBCL的大型基于阵列的表达数据集。我们的研究表明，miR-155的表达与DLBCL的特定分子亚群分离，并且在活化B细胞（ABC）型淋巴瘤中最高。这些肿瘤的特征在于NF-κ B信号的组成性激活，这支持了来自我们细胞系的数据。更重要的是，使用监督学习算法，我们确定了由miR-155的差异表达驱动的强大基因签名。这些谱包含几种基因标记物，包括预测的靶点，在表达高水平miR-155的肿瘤中一致下调。我们的数据开始揭示miR-155在DLBCL中表达的全基因组效应，并表明这种策略在识别和验证miRNA靶基因中的实用性。(c)2008年爱思唯尔公司All rights reserved.
MicroRNAs (miRNAs) attenuate gene expression by pairing to the 3'UTR of target transcripts inducing RNA cleavage or translational inhibition. Overexpression of microRNA-155 (miR-155), measured either at the primary (BIC gene) or mature transcript level, was recently described in diffuse large B-cell lymphomas (DLBCL). These studies have been limited in size, however, and have not attempted to link miR-155 expression to that of putative target genes. To start to address these issues, we examined a collection of 22 well-characterized DLBCL cell lines. The expression of miR-155 is heterogeneous in these cell lines and associates with NF-kappa B activity. We found that the expression of the primary miR-155 transcript reliably reflects that of the functional mature miR-155. Because many gene array platforms include probe sets for the primary miR-155 sequences, these findings allowed us to confidently examine large array-based expression datasets of primary DLBCLs in the context of miR-155 levels. Our investigation revealed that miR-155 expression segregates with specific molecular subgroups of DLBCL and it is highest in activated B-cell (ABC)-type lymphomas. These tumors are characterized by constitutive activation of NF-kappa B signals, which supports the data derived from our cell lines. More importantly, using supervised learning algorithms, we identified a robust gene signature driven by the differential expression of miR-155. These profiles contained several gene markers, including predicted targets, consistently downregulated in tumors expressing high levels of miR-155. Our data start to unveil the genome-wide effects of miR-155 expression in DLBCL and indicate the utility of this strategy in the identification and validation of miRNA target genes. (c) 2008 Elsevier Inc. All rights reserved.