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Robustness and backbone motif of a cancer network regulated by miR-17-92 cluster during the G1/S transition.

Yang L, Meng Y, Bao C, Liu W, Ma C, Li A, Xuan Z, Shan G, Jia Y - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biophysics and Department of Physics, Central China Normal University, Wuhan, China.

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.

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Mammalian cancer cell network during G1/s transition (MGSTR network).The 8-node network is constructed on the basis of previous experimental results [17]–[22]. The circular nodes represent oncogene, the octagon nodes represent tumor suppressors, and the quadrilateral nodes represent oncogenes or tumor suppressors. Green arrow represents active interactions, and the blue (or black) hammerheads represent inhibitory interactions.
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pone-0057009-g001: Mammalian cancer cell network during G1/s transition (MGSTR network).The 8-node network is constructed on the basis of previous experimental results [17]–[22]. The circular nodes represent oncogene, the octagon nodes represent tumor suppressors, and the quadrilateral nodes represent oncogenes or tumor suppressors. Green arrow represents active interactions, and the blue (or black) hammerheads represent inhibitory interactions.

Mentions: Basing on the interactions between the regulatory factors and the miRNAs [19], we have constructed a Boolean model of the mammalian G1/S transition regulatory network (MGSTR network) involving oncogenes, tumor suppressor genes, and miR-17-92, as shown in Fig. 1. This structure contains eight nodes (each node represents a regulatory element) and seventeen lines (each line represents an interaction between nodes). There is often a threshold for the functional copy number of individual molecule in biochemical reactions. Copy number of the gene products higher or lower than the threshold can be represented by two different states: on or off. Therefore, the expression of genes can be considered as a total-or-nothing process, that is, a binary switch which has only two states 1 and 0.


Robustness and backbone motif of a cancer network regulated by miR-17-92 cluster during the G1/S transition.

Yang L, Meng Y, Bao C, Liu W, Ma C, Li A, Xuan Z, Shan G, Jia Y - PLoS ONE (2013)

Mammalian cancer cell network during G1/s transition (MGSTR network).The 8-node network is constructed on the basis of previous experimental results [17]–[22]. The circular nodes represent oncogene, the octagon nodes represent tumor suppressors, and the quadrilateral nodes represent oncogenes or tumor suppressors. Green arrow represents active interactions, and the blue (or black) hammerheads represent inhibitory interactions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585929&req=5

pone-0057009-g001: Mammalian cancer cell network during G1/s transition (MGSTR network).The 8-node network is constructed on the basis of previous experimental results [17]–[22]. The circular nodes represent oncogene, the octagon nodes represent tumor suppressors, and the quadrilateral nodes represent oncogenes or tumor suppressors. Green arrow represents active interactions, and the blue (or black) hammerheads represent inhibitory interactions.
Mentions: Basing on the interactions between the regulatory factors and the miRNAs [19], we have constructed a Boolean model of the mammalian G1/S transition regulatory network (MGSTR network) involving oncogenes, tumor suppressor genes, and miR-17-92, as shown in Fig. 1. This structure contains eight nodes (each node represents a regulatory element) and seventeen lines (each line represents an interaction between nodes). There is often a threshold for the functional copy number of individual molecule in biochemical reactions. Copy number of the gene products higher or lower than the threshold can be represented by two different states: on or off. Therefore, the expression of genes can be considered as a total-or-nothing process, that is, a binary switch which has only two states 1 and 0.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biophysics and Department of Physics, Central China Normal University, Wuhan, China.

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.

Show MeSH
Related in: MedlinePlus