Effects Of Feedback On Noise And Noise Propagation In Tumor Cells

The effect of noise in a gene regulatory network on its network cannot be ignored.And when the system is perturbed by noise,it is crucial to ensure the reliable transmission of information in the network.Feedback is a pervasive control mechanism in regulatory networks,and coupled feedback loops have an important role in the propagation of noise in the network.Therefore,the study of the effect of coupling feedback on noise propagation has become one of the important elements of biophysical research.In this paper,the effects of different feedbacks on the stochastic dynamics behavior and noise propagation mechanisms in biological systems are investigated for unidirectional and bidirectional transition cascades,using stochastic dynamics theory as well as computer simulation techniques:(1)Effects of coupled feedback on noise and noise propagation in colon cancer cells.The phenotypic transition cascade of colon cancer cells contains three compartments: stem cells(SCs),transiently expanded cells(TACs),and fully differentiated cells(FDCs).To maintain the in vivo homeostasis between cells,the differentiation rate of stem cells and transiently expanded cells must be regulated by pure linear(Linear,abbreviated as L)feedback or saturatin(abbreviated as S)feedback.These two types of feedback are coupled with each other to form four types of feedback:LL,LS,SL,and SS.With the help of signal sensitivity coefficients,equations for linear noise approximation,logarithmic gain,noise propagation,and noise amplification are derived to investigate the effects of the four types of feedback on noise as well as noise propagation.The results show that SL feedback and SS feedback have obvious advantages:(i)The characteristics of steady-state changes in their cell populations are more consistent with the tumor development process.(ii)The degree of correlation between cell fluctuation has a minimum value,that is,reasonable adjustment of parameters can effectively use or destroy the strong correlation between them.(iii)Although there is no direct interaction between stem cells and fully differentiated cells,the noise from stem cells can still propagate to fully differentiated cells through transient expansion of cells.Therefore,SL feedback or SS feedback might be a better option to adjust the differentiation of SCs and TACs and would be more consistent with the evolutionary and selective diversity of organisms from simple to complex.(2)Study of noise signal propagation mechanisms in the bidirectional phenotypic transition cascade.The bidirectional phenotypic transition cascade consists of normal cells and holding cells.In response to environmental triggers,cells can switch between the two phenotypes,and the presence of persistent cells is one of the reasons for recurrent infections.To treat recurrent infections,a gain coefficient is introduced with the help of the signal gain concept in signals and systems.The gain-fluctuation equation was obtained by a linear noise approximation of the master equation.Numerical simulations of the equation revealed that:(i)The interconversion between two phenotypes can directly generate interconversion noise,which is usually very small and almost negligible.(ii)The interconversion can also provide a global fluctuating environment and thus indirectly generate additional intrinsic noise,which is a major part of the total noise.It can be seen that the indirect effect of interconversion is much greater than its direct effect,which provides a theoretical idea for the treatment of recurrent infections caused by holding cells.