Robustness and Backbone Motif of a Cancer Network Regulated by miR-17-92 Cluster during the G1/S Transition

Abstract

Based on interactions among transcription factors, oncogenes, tumor suppressors and microRNAs, a Boolean model of cancer network regulated by miR-17-92 cluster is constructed, and the network is associated with the control of G1/S transition in the mammalian cell cycle. The robustness properties of this regulatory network are investigated by virtue of the Boolean network theory. It is found that, during G1/S transition in the cell cycle process, the regulatory networks are robustly constructed, and the robustness property is largely preserved with respect to small perturbations to the network. By using the unique process-based approach, the structure of this network is analyzed. It is shown that the network can be decomposed into a backbone motif which provides the main biological functions, and a remaining motif which makes the regulatory system more stable. The critical role of miR-17-92 in suppressing the G1/S cell cycle checkpoint and increasing the uncontrolled proliferation of the cancer cells by targeting a genetic network of interacting proteins is displayed with our model. © 2013 Yang et al.