基于let7-LIN28双稳态现象的动力学建模与抗耐药策略分析
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摘要
目的探究不同参数对癌细胞中let7-LIN28负反馈系统双稳态性质的影响,以求找到对该双稳态系统影响较大的参数,为调节治疗时产生的细胞耐药性提供思路。方法通过动力学建模研究二维系统双稳态,通过绘制系统零线图观察系统双稳态特性随参数取值改变而发生的变化。结果各参数对系统双稳态特性的影响程度存在差异,改变参数取值可以调节系统的双稳态特性,甚至可以实现双稳态与单稳态的切换。结论对敏感度较高的参数进行有针对性的调节可以达到控制细胞耐药性的目的。
Objective To find the key factors that have great influences on the bistable properties between let7 and LIN28 by exploring the effects of different parameters on the negative feedback bistable system, and provide insights for regulating the drug resistance generated during treatment. Methods The bistability of two-dimensional system was studied by dynamics modeling, and the influence of the parameters on stability behavior of the system was investigated from the portrait of nullclines. Results The parameters showed heterogeneous effects on bistability behavior of the system. A shift in parameter values could regulate the characteristics of bistability and might even make a switch back and forth between bistability and monostability. Conclusions Targeted regulation of sensitive parameters can potentially achieve the goal of controlling drug resistance.
Objective To find the key factors that have great influences on the bistable properties between let7 and LIN28 by exploring the effects of different parameters on the negative feedback bistable system, and provide insights for regulating the drug resistance generated during treatment. Methods The bistability of two-dimensional system was studied by dynamics modeling, and the influence of the parameters on stability behavior of the system was investigated from the portrait of nullclines. Results The parameters showed heterogeneous effects on bistability behavior of the system. A shift in parameter values could regulate the characteristics of bistability and might even make a switch back and forth between bistability and monostability. Conclusions Targeted regulation of sensitive parameters can potentially achieve the goal of controlling drug resistance.
引文
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[2] FUNG YC.Biomechanics:Motion,flow,stress,and growth [M].New York:Springer,1990.
[3] AGUDA BD,KIM Y,PIPER-HUNTER MG,et al.MicroRNA regulation of a cancer network:Consequences of the feedback loops involving miR-17-92,E2F,and Myc [J].PNAS,2008,105(50):19678-19683.
[4] WEI HC.A mathematical model of tumour growth with Beddington-DeAngelis functional response:A case of cancer without disease [J].J Biol Dyn,2018,12(1):194-210.
[5] ITIK M,BANKS SP.Chaos in a three-dimensional cancer model [J].Int J Bifurcat Chaos,2010,20(1):71-79.
[6] DEPILLIS LG,GU W,RADUNSKAYA AE.Mixed immunotherapy and chemotherapy of tumors:Modeling,applications and biological interpretations [J].J Theor Biol,2006,238:841-862.
[7] 梁静,廖娟,杨怡萍.Lin28-let7信号通路和下游靶基因在食管癌中的表达及其临床意义[J].现代肿瘤医学,2013,21(10):2161-2165.
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