Widespread microRNA repression by Myc contributes to tumorigenesis
Widespread microRNA repression by Myc contributes to tumorigenesis
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DOI：
10.1038/ng.2007.30
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发表时间：
2008-01-01
期刊：
影响因子：
30.8
通讯作者：
Mendell, Joshua T.
中科院分区：
文献类型：
--
作者：
Chang, Tsung-Cheng;Yu, Duonan;Mendell, Joshua T.
致癌转录因子c - Myc（Myc）在许多人类恶性肿瘤中发生病理性激活。已知Myc可直接上调一组促肿瘤发生的微小RNA（miRNAs），即miR - 17 - 92簇。通过对人类和小鼠B细胞淋巴瘤模型的分析，我们在此表明，Myc调控的miRNAs集合比之前预期的要广泛得多。出乎意料的是，Myc激活的主要结果是miRNA表达的广泛抑制。染色质免疫沉淀显示，这种抑制在很大程度上可能是Myc与miRNA启动子结合的直接结果。我们进一步表明，受抑制的miRNAs的强制表达会降低淋巴瘤细胞的致瘤潜能。这些结果表明，Myc对miRNA转录组的广泛重编程有助于肿瘤发生。
The c-Myc oncogenic transcription factor (Myc) is pathologically activated in many human malignancies. Myc is known to directly upregulate a pro-tumorigenic group of microRNAs (miRNAs) known as the miR-17 - 92 cluster. Through the analysis of human and mouse models of B cell lymphoma, we show here that Myc regulates a much broader set of miRNAs than previously anticipated. Unexpectedly, the predominant consequence of activation of Myc is widespread repression of miRNA expression. Chromatin immunoprecipitation reveals that much of this repression is likely to be a direct result of Myc binding to miRNA promoters. We further show that enforced expression of repressed miRNAs diminishes the tumorigenic potential of lymphoma cells. These results demonstrate that extensive reprogramming of the miRNA transcriptome by Myc contributes to tumorigenesis.