Long noncoding RNA EMS connects c-Myc to cell cycle control and tumorigenesis
Long noncoding RNA EMS connects c-Myc to cell cycle control and tumorigenesis
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长非编码RNA EMS将c-Myc与细胞周期控制和肿瘤发生联系起来
DOI：
10.1073/pnas.1903432116
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发表时间：
2019-07-16
影响因子：
11.1
通讯作者：
Mei, Yide
中科院分区：
文献类型：
--
作者：
Wang, Chenfeng;Yang, Yang;Mei, Yide
作为最重要的致癌基因之一，c-Myc在超过一半的人类癌症中被激活。c-Myc的致癌功能很大程度上归因于其作为主转录因子的内在性质。长链非编码rna （lncRNAs）的失调与包括癌症在内的多种人类疾病有关。然而，lncRNA在调节c-Myc致癌活性中的作用尚不清楚。在这里，我们报道了作为c-Myc的转录靶点，lncRNA E2F1信使RNA （mRNA）稳定因子通过调节E2F1 mRNA的稳定性来调节c-Myc的功能。这项研究为c-Myc促进肿瘤发生的机制提供了见解。c-Myc的不正常表达是癌症的一个重要分子标志。c-Myc的致癌功能很大程度上归因于其作为主转录因子的内在性质。在这里，我们报道了长链非编码RNA (lncRNA) E2F1信使RNA （mRNA）稳定因子（EMS）作为c-Myc的直接转录靶点。EMS作为一种致癌分子，通过促进G1/S细胞周期进程发挥作用。在机制上，EMS与RNA结合蛋白RALY协同稳定E2F1 mRNA，从而增加E2F1的表达。此外，EMS能够通过调节E2F1 mRNA的稳定性将c-Myc与细胞周期控制和肿瘤发生联系起来。总之，这些发现揭示了c-Myc诱导E2F1表达的一个以前未被认识的机制，也暗示了EMS在调节c-Myc功能中起重要作用。
Significance As one of the most important oncogenes, c-Myc is activated in over half of human cancers. The oncogenic function of c-Myc has been largely attributed to its intrinsic nature as a master transcription factor. Dysregulation of long noncoding RNAs (lncRNAs) has been implicated in a variety of human diseases, including cancer. However, the function of lncRNA in the regulation of c-Myc oncogenic activity is still not well understood. Here, we report that as a transcriptional target of c-Myc, lncRNA E2F1 messenger RNA (mRNA) stabilizing factor regulates c-Myc function via modulating E2F1 mRNA stability. This study provides insights into the mechanisms of how c-Myc promotes tumorigenesis. Deregulated expression of c-Myc is an important molecular hallmark of cancer. The oncogenic function of c-Myc has been largely attributed to its intrinsic nature as a master transcription factor. Here, we report the long noncoding RNA (lncRNA) E2F1 messenger RNA (mRNA) stabilizing factor (EMS) as a direct c-Myc transcriptional target. EMS functions as an oncogenic molecule by promoting G1/S cell cycle progression. Mechanistically, EMS cooperates with the RNA binding protein RALY to stabilize E2F1 mRNA, and thereby increases E2F1 expression. Furthermore, EMS is able to connect c-Myc to cell cycle control and tumorigenesis via modulating E2F1 mRNA stability. Together, these findings reveal a previously unappreciated mechanism through which c-Myc induces E2F1 expression and also implicate EMS as an important player in the regulation of c-Myc function.