Toward a system-level understanding of microRNA pathway via mathematical modeling.

The microRNA (miRNA) pathway plays multiple roles in regulating mechanisms controlling both physiological and pathological processes such as the cell proliferation and cancers. But little is known about the dynamic properties, key rate-limiting steps as well as the stochastic noise in this pathway. Presently, a system-theoretic approach was presented to analyze and quantitative modeling of a generic miRNA pathway, which can be implemented deterministically and stochastically. Our results show that the inferred dynamic properties obtained from the mathematical models of the miRNA pathway are well consistent with previous experimental observations. By sensitivity analysis, the key steps in this pathway were found to be the miRNA gene transcription, RISC decay and mRNA formation. In addition, the results of quantified noise strength along the pathway demonstrate that the pathway can reduce the ingress noise and reveal the noise robustness property. Our findings also present testable hypothesis for experimental biologists to further investigate miRNA's increasing functional roles in regulating various cellular processes. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.