Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA 02142, USA.
Institute of Mathematics, University of the Philippines, Diliman, Quezon City 1101 Philippines.
Sci Rep. 2016 Sep 9;6:32823. doi: 10.1038/srep32823.
The restriction point marks a switch in G1 from growth factor-dependent to growth factor-independent progression of the cell cycle. The proper regulation of this switch is important for normal cell processes; aberrations could result in a number of diseases such as cancer, neurodegenerative disorders, stroke and myocardial infarction. To further understand the regulation of the restriction point, we extended a mathematical model of the Rb-E2F pathway to include members of the microRNA cluster miR-17-92. Our mathematical analysis shows that microRNAs play an essential role in fine-tuning and providing robustness to the switch. We also demonstrate how microRNA regulation can steer cells in or out of cancer states.
限制点标志着细胞周期从生长因子依赖到生长因子非依赖的 G1 转换。这个开关的适当调节对于正常细胞过程很重要；异常可能导致多种疾病，如癌症、神经退行性疾病、中风和心肌梗死。为了进一步了解限制点的调节，我们扩展了 Rb-E2F 途径的数学模型，纳入了 microRNA 簇 miR-17-92 的成员。我们的数学分析表明，microRNA 在微调和提供开关的鲁棒性方面起着至关重要的作用。我们还展示了 microRNA 调节如何引导细胞进入或离开癌症状态。
