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首页> 外文期刊>BMC Genomics >miRConnect 2.0: identification of oncogenic, antagonistic miRNA families in three human cancers
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miRConnect 2.0: identification of oncogenic, antagonistic miRNA families in three human cancers

机译：miRConnect 2.0：鉴定三种人类癌症中的致癌性，拮抗性miRNA家族

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Background Based on their function in cancer micro(mi)RNAs are often grouped as either tumor suppressors or oncogenes. However, miRNAs regulate multiple tumor relevant signaling pathways raising the question whether two oncogenic miRNAs could be functional antagonists by promoting different steps in tumor progression. We recently developed a method to connect miRNAs to biological function by comparing miRNA and gene array expression data from the NCI60 cell lines without using miRNA target predictions (miRConnect). Results We have now extended this analysis to three primary human cancers (ovarian cancer, glioblastoma multiforme, and kidney renal clear cell carcinoma) available at the Cancer Genome Atlas (TCGA), and have correlated the expression of the clustered miRNAs with 158 oncogenic signatures (miRConnect 2.0). We have identified functionally antagonistic groups of miRNAs. One group (the agonists), which contains many of the members of the miR-17 family, correlated with c-Myc induced genes and E2F gene signatures. A group that was directly antagonistic to the agonists in all three primary cancers contains miR-221 and miR-222. Since both miR-17?~?92 and miR-221/222 are considered to be oncogenic this points to a functional antagonism of different oncogenic miRNAs. Analysis of patient data revealed that in certain patients agonistic miRNAs predominated, whereas in other patients antagonists predominated. In glioblastoma a high ratio of miR-17 to miR-221/222 was predictive of better overall survival suggesting that high miR-221/222 expression is more adverse for patients than high miR-17 expression. Conclusion miRConnect 2.0 is useful for identifying activities of miRNAs that are relevant to primary cancers. The new correlation data on miRNAs and mRNAs deregulated in three primary cancers are available at miRConnect.org
机译：背景技术基于它们在癌症中的功能，micro（mi）RNA通常被归类为肿瘤抑制因子或致癌基因。然而，miRNA调节多种与肿瘤相关的信号通路，这引发了两个致癌miRNA是否可以通过促进肿瘤进展的不同步骤而成为功能性拮抗剂的问题。我们最近开发了一种通过比较来自NCI60细胞系的miRNA和基因阵列表达数据而无需使用miRNA靶标预测（miRConnect）的方法来将miRNA连接到生物学功能的方法。结果我们现在已将这项分析扩展到癌症基因组图谱（TCGA）可获得的三种主要人类癌症（卵巢癌，多形性胶质母细胞瘤和肾肾透明细胞癌），并将簇状miRNA的表达与158个致癌特征相关联（ miRConnect 2.0）。我们已经确定了miRNA的功能拮抗基团。一组（激动剂）包含许多miR-17家族成员，与c-Myc诱导的基因和E2F基因签名相关。在所有三种原发性癌症中均直接拮抗激动剂的组包含miR-221和miR-222。由于miR-17？〜？92和miR-221 / 222均被认为是致癌的，因此这表明了不同致癌miRNA的功能拮抗作用。对患者数据的分析表明，在某些患者中，激动性miRNA占主导地位，而在其他患者中，拮抗剂则占主导地位。在胶质母细胞瘤中，较高的miR-17与miR-221 / 222的比例预示着更好的总体存活率，这表明较高的miR-221 / 222表达对患者比较高的miR-17表达更不利。结论miRConnect 2.0可用于鉴定与原发癌相关的miRNA活性。 miRConnect.org提供了有关在三种原发性癌症中失控的miRNA和mRNA的新相关数据。

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