Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway
Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway
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DOI：
10.1182/blood-2010-10-315432
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发表时间：
2011-06-09
期刊：
影响因子：
20.3
通讯作者：
Malumbres, Marcos
中科院分区：
文献类型：
--
作者：
Bueno, Mara J.;Gomez de Cedron, Marta;Malumbres, Marcos
许多哺乳动物转录本含有多个 miRNA 的靶位点，但目前尚不清楚 miRNA 可以在多大程度上协调调节单个基因。我们绘制了小鼠和人类淋巴瘤中下调的 miRNA 与过度表达的靶蛋白编码基因之间的相互作用。 Myc 是这些淋巴瘤的标志性癌基因之一，是小鼠淋巴瘤中与下调 miRNA 发生最多遗传相互作用的上调基因。细胞和报告基因检测证实了其中几种 miRNA 对 Myc 的调节。同样的方法将 MYC 和多个 Myc 靶点确定为人伯基特淋巴瘤（一种以 MYC 癌基因易位为特征的病理学特征）中下调 miRNA 的优先靶点。这些结果表明，必须协调下调多个 miRNA 才能增强关键癌基因，例如 Myc。其中一些靶向 Myc 的 miRNA 被 Myc 抑制，表明这些肿瘤是 Myc 与 miRNA 活性不平衡的结果。 （血。2011；117（23）：6255-6266）
Many mammalian transcripts contain target sites for multiple miRNAs, although it is not clear to what extent miRNAs may coordinately regulate single genes. We have mapped the interactions between down-regulated miRNAs and overexpressed target protein-coding genes in murine and human lymphomas. Myc, one of the hallmark oncogenes in these lymphomas, stands out as the up-regulated gene with the highest number of genetic interactions with down-regulated miRNAs in mouse lymphomas. The regulation of Myc by several of these miRNAs is confirmed by cellular and reporter assays. The same approach identifies MYC and multiple Myc targets as a preferential target of down-regulated miRNAs in human Burkitt lymphoma, a pathology characterized by translocated MYC oncogenes. These results indicate that several miRNAs must be coordinately down-regulated to enhance critical oncogenes, such as Myc. Some of these Myc-targeting miRNAs are repressed by Myc, suggesting that these tumors are a consequence of the unbalanced activity of Myc versus miRNAs. (Blood. 2011; 117(23): 6255-6266)