The E2F3-Oncomir-1 axis is activated in Wilms' tumor
The E2F3-Oncomir-1 axis is activated in Wilms' tumor
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DOI：
10.1158/0008-5472.can-08-0592
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发表时间：
2008-06-01
期刊：
影响因子：
11.2
通讯作者：
Teh, Bin T.
中科院分区：
文献类型：
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作者：
Kort, Eric J.;Farber, Leslie;Teh, Bin T.
Oncomir-1是位于13号染色体上的致癌microRNA（miRNA）簇。以前的体外研究表明，它是由转录因子E2 F3的转录调控。在这份报告中，我们结合联合收割机的表达谱的mRNA和miRNA在肾母细胞瘤（WT）样本提供的第一个证据表明，E2 F3-Oncomir-1轴，以前确定在细胞培养中，是失调的原发性人类肿瘤。RNA表达特征的分析显示，与其他肾肿瘤相比，E2 F3基因特征在分析的所有WT样品中被激活。这一发现在蛋白质水平上通过免疫组织化学进行了验证。E2 F3在早期肿瘤中表达最低，在转移组织中表达最高。WT中miRNA的表达谱显示，相对于其他肾脏肿瘤亚型，Oncomir-1家族的每个测量成员的表达在WT中最高。定量PCR证实这些miRNAs在WT中相对于正常肾组织过表达。这些结果表明E2 F3-Oncomir-1轴在WT中被激活。我们的研究还显示了整合基因组学结合基因签名分析与miRNA表达谱的实用性，以确定在疾病状态下受到干扰的蛋白质-miRNA相互作用。
Oncomir-1 is an oncogenic cluster of microRNAs (miRNA) located on chromosome 13. Previous in vitro studies showed that it is transcriptionally regulated by the transcription factor E2F3. In this report, we combine expression profiling of both mRNA and miRNAs in Wilms' tumor (WT) samples to provide the first evidence that the E2F3-Oncomir-1 axis, previously identified in cell culture, is deregulated in primary human tumors. Analysis of RNA expression signatures showed that an E2F3 gene signature was activated in all WT samples analyzed, in contrast to other kidney tumors. This finding was validated by immunohistochemistry on the protein level. Expression of E2F3 was lowest in early-stage tumors and highest in metastatic tissue. Expression profiling of miRNAs in WT showed that expression of each measured member of the Oncomir-1 family was highest in WT relative to other kidney tumor subtypes. Quantitative PCR confirmed that these miRNAs were overexpressed in WT relative to normal kidney tissue. These results suggest that the E2F3-Oncomir-1 axis is activated in WT. Our study also shows the utility of integrated genomics combining gene signature analysis with miRNA expression profiling to identify protein-miRNA interactions that are perturbed in disease states.