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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Microrna Regulation Of A Cancer Network: Consequences Of The Feedback Loops Involving Mir-17-92, E2f, And Myc
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Microrna Regulation Of A Cancer Network: Consequences Of The Feedback Loops Involving Mir-17-92, E2f, And Myc

机译：癌症网络的Microrna调节：涉及Mir-17-92，E2f和Myc的反馈回路的后果

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摘要

The transcription factors E2F and Myc participate in the control of cell proliferation and apoptosis, and can act as oncogenes or tumor suppressors depending on their levels of expression. Positive feedback loops in the regulation of these factors are predicted-and recently shown experimentally-to lead to testability, which is a phenomenon characterized by the existence of tow and high protein levels ("off" and "on" levels, respectively), with sharp transitions between levels being inducible by, for example, changes in growth factor concentrations. E2F and Myc are inhibited at the posttranscrip-tional step by members of a cluster of microRNAs (miRs) called miR-17-92. In return, E2F and Myc induce the transcription of miR-17-92, thus forming a negative feedback loop in the interaction network. The consequences of the coupling between the E2F/Myc positive feedback loops and the E2F/Myc/miR-17-92 negative feedback loop are analyzed using a mathematical model. The model predicts that miR-17-92 plays a critical role in regulating the position of the off-on switch in E2F/Myc protein levels, and in determining the on levels of these proteins. The model also predicts large-amplitude protein oscillations that coexist with the off steady state levels. Using the concept and model prediction of a "cancer zone," the oncogenic and tumor suppressor properties of miR-17-92 is demonstrated to parallel the same properties of E2F and Myc.
机译：转录因子E2F和Myc参与细胞增殖和凋亡的控制，并可以根据其表达水平充当癌基因或抑癌基因。预测到了这些因素的调节中的正反馈回路，并且最近在实验中得到了证明，这导致了可测试性，这种现象的特征是存在丝束和高蛋白水平（分别为“关闭”和“开启”水平），并且通过例如生长因子浓度的变化可以诱导水平之间的急剧转变。 E2F和Myc在转录后步骤被称为miR-17-92的microRNA（miR）簇成员抑制。作为回报，E2F和Myc诱导miR-17-92的转录，从而在相互作用网络中形成一个负反馈环。使用数学模型分析了E2F / Myc正反馈回路与E2F / Myc / miR-17-92负反馈回路之间耦合的结果。该模型预测，miR-17-92在调节E2F / Myc蛋白水平中的断开开关的位置以及确定这些蛋白的水平中起关键作用。该模型还预测与稳态稳态水平共存的大振幅蛋白质振荡。使用“癌区”的概念和模型预测，证明miR-17-92的致癌和抑癌特性与E2F和Myc的相同特性平行。

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