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A Study On Kinetics Of Gene Regulatory And G1/S Transition Of Cancer Cell By Non-coding RNA

Posted on:2014-01-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:W H LiuFull Text:PDF
GTID:1220330398982218Subject:Theoretical Physics
Abstract/Summary:PDF Full Text Request
Gene expression and regulation is one of the code problems of modern molecular biology. A lot of researchs show non-coding RNAs (ncRNA) have important function as the genes which code for proteins. There is one kind of non-coding RNA called MicroRNA,19-22nt in length, existing in eukaryote which can inhibit the post-transcriptional gene regulation by binding with its target messenger RNA specifically. The essence of life phenomena and process is the interaction between biological molecules (DNA, RNA, protein, etc.), but this interaction is characteristic and complicated. On the molecular level, the interaction between biological molecules is occasional events of molecular reaction; nevertheless, various vital movements have been regulated in time and space on the network level. The problems about the internal relation between biological function and network structure with a high degree of randomness on the stochastic level and stability on the network level is a scientific problem of life science currently.In this paper we study the theory of non-coding RNA regulated by noise on the stochastic level, the network evolution and the interaction between network structure and biological function that of cancer cell G1/S transition regulated by non-coding RNA on the network level; and discuss the vibrational resonance phenomena induced by transition of phase-locking modes in excitable systems. The details of these works are as follows:First, we use the chemical Langevin method to deduce the formula of intrinsic noise of RNA molecules in post-transcriptional gene regulation by small non-coding RNA (fano factor) based on two regulatory modes (single mRNA regulated by one ncRNA and two mRNA regulated by on ncRNA). It is found that the expression of target mRNA will appear RNA interference (RNAi) phenomena with the increasing of small ncRNA’s transcription rate when the the transcription rate of mRNA is fixed; For the regulation of single target mRNA, the intrinsic noise of target mRNA and ncRNA approaches the bare poissonian limit in the regimen of RNAi and expression; For the regulation of two target mRNAs, the intrinsic noise intensity of ncRNA and mRNA will appear a maximum value with the increasing of transcription rate of mRNA in the regimen of crossover.Then, based on the interaction of transcription factor, oncogene, tumor suppressor and miRNA, we construct a boolean network model of cancer cell regulated by miR-17-92gene cluster which plays a very important role in the regulation of the G1/S checkpoint of mammalian cell. By using this regulatory network, we study the stability (or robustness) of the network, it is found that there is a very strong stability in the G1/S transition even if every gene of the network has a strong random switch in the cell cycle; comparing with the experimental results, we find that the real biological pathway of cell G1/S transition corresponds to the trajectory of the biggest attractor of the network system. This network also can be decomposed into a backbone part which provides the main biological functions, and a remaining part which makes the network more stable by using a process-based method; we also find that the miR-17-92cluster is very important in the network structure.Finally, we study the Occurrence and mechanism of vibrational resonance in the excitable systems, a single vibrational resonance and a vibrational bi-resonance will appear when we tune the amplitude and frequency of the high-frequency force simultaneously; by using the phase diagram of low-frequency FitzHugh-Nagumo model, it is found that every maxima of response measure is located at the transition boundary of phase patterns; the results show that the transition between different phase-locking modes induces vibrational resonance in the excitable systems; this mechanism is also proved in the Hodgkin-Huxley neural model. These results provide a potential valuable application for the transmission of weak signals in nonlinear systems.
Keywords/Search Tags:gene expression, gene regulation nework, non-coding RNA, Langevin theory, Boolean netwoik, vibrational resonance
PDF Full Text Request
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