Bui Thi V, Mendell Joshua T
Howard Hughes Medical Institute and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Genes Cancer. 2010 Jun 1;1(6):568-575. doi: 10.1177/1947601910377491.
Hyperactivity of the Myc oncogenic transcription factor dramatically reprograms gene expression to facilitate cellular proliferation and tumorigenesis. To elicit these effects, Myc coordinates the activation and repression of an extensive network of protein-coding genes and, as has recently been appreciated, noncoding RNAs including microRNAs (miRNAs). Consistent with their ability to potently influence cancer phenotypes, the regulation of miRNAs by Myc affects virtually all aspects of the Myc oncogenic program, including proliferation, survival, metabolism, angiogenesis, and metastasis. This review will summarize the current understanding of the mechanisms underlying Myc-dependent transcriptional and posttranscriptional control of miRNAs and the resultant effects on tumorigenesis. As miRNAs are integral nodes in the transcriptional network controlled by Myc, modulating their activity represents a promising new approach for cancer therapy.
Myc致癌转录因子的过度活跃会显著重编程基因表达,以促进细胞增殖和肿瘤发生。为了引发这些效应,Myc协调了一个由蛋白质编码基因以及最近发现的包括微小RNA(miRNA)在内的非编码RNA组成的广泛网络的激活和抑制。与它们有效影响癌症表型的能力一致,Myc对miRNA的调控几乎影响了Myc致癌程序的所有方面,包括增殖、存活、代谢、血管生成和转移。本综述将总结目前对Myc依赖的miRNA转录和转录后调控机制以及对肿瘤发生的影响的理解。由于miRNA是Myc控制的转录网络中的重要节点,调节它们的活性代表了一种有前景的癌症治疗新方法。