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Gene regulation is governed by a core network in hepatocellular carcinoma.

Gu Z, Zhang C, Wang J - BMC Syst Biol (2012)

Bottom Line: However, with the development of high-throughput technologies it is possible to gain a systematic view of biological systems to enhance the understanding of the roles of genes associated with HCC.We found that microRNAs mainly control biological functions related to mitochondria and oxidative reduction, while transcription factors control immune responses, extracellular activity and the cell cycle.In particular, we highlight the importance of the core gene regulatory network; we propose that it is highly related to HCC and we believe further experimental validation is worthwhile.

View Article: PubMed Central - HTML - PubMed

Affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, China.

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and the mechanisms that lead to the disease are still relatively unclear. However, with the development of high-throughput technologies it is possible to gain a systematic view of biological systems to enhance the understanding of the roles of genes associated with HCC. Thus, analysis of the mechanism of molecule interactions in the context of gene regulatory networks can reveal specific sub-networks that lead to the development of HCC.

Results: In this study, we aimed to identify the most important gene regulations that are dysfunctional in HCC generation. Our method for constructing gene regulatory network is based on predicted target interactions, experimentally-supported interactions, and co-expression model. Regulators in the network included both transcription factors and microRNAs to provide a complete view of gene regulation. Analysis of gene regulatory network revealed that gene regulation in HCC is highly modular, in which different sets of regulators take charge of specific biological processes. We found that microRNAs mainly control biological functions related to mitochondria and oxidative reduction, while transcription factors control immune responses, extracellular activity and the cell cycle. On the higher level of gene regulation, there exists a core network that organizes regulations between different modules and maintains the robustness of the whole network. There is direct experimental evidence for most of the regulators in the core gene regulatory network relating to HCC. We infer it is the central controller of gene regulation. Finally, we explored the influence of the core gene regulatory network on biological pathways.

Conclusions: Our analysis provides insights into the mechanism of transcriptional and post-transcriptional control in HCC. In particular, we highlight the importance of the core gene regulatory network; we propose that it is highly related to HCC and we believe further experimental validation is worthwhile.

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Core gene regulatory network. Different colors represent the different modules to which the nodes belong. The color for each module is the same as the color illustrated in Figure 3. Black edges represent the interactions are supported by experiments.
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Figure 5: Core gene regulatory network. Different colors represent the different modules to which the nodes belong. The color for each module is the same as the color illustrated in Figure 3. Black edges represent the interactions are supported by experiments.

Mentions: The core GRN is the sub-network extracted from the global GRN, where the nodes in the core GRN are only TFs and miRNAs. Edges in core GRN have the highest edge-betweenness (larger than 99 % quantile) calculated from the global GRN. Edge-betweenness is defined by the number of shortest paths going through an edge in the network, and in the context of GRN, edge-betweenness measures the number of targets that a regulation would affect. In the core GRN, there were 32 nodes and 42 edges. Among them, nine interactions have been supported by previous experiments. In particular, 17 additional experimentally-supported interactions can be inferred from the core GRN indirectly (the list can be found in Additional File 3). The core GRN is illustrated in Figures 3 and 5, and the adjacent list of core GRN can be found in Additional File 4.


Gene regulation is governed by a core network in hepatocellular carcinoma.

Gu Z, Zhang C, Wang J - BMC Syst Biol (2012)

Core gene regulatory network. Different colors represent the different modules to which the nodes belong. The color for each module is the same as the color illustrated in Figure 3. Black edges represent the interactions are supported by experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3403900&req=5

Figure 5: Core gene regulatory network. Different colors represent the different modules to which the nodes belong. The color for each module is the same as the color illustrated in Figure 3. Black edges represent the interactions are supported by experiments.
Mentions: The core GRN is the sub-network extracted from the global GRN, where the nodes in the core GRN are only TFs and miRNAs. Edges in core GRN have the highest edge-betweenness (larger than 99 % quantile) calculated from the global GRN. Edge-betweenness is defined by the number of shortest paths going through an edge in the network, and in the context of GRN, edge-betweenness measures the number of targets that a regulation would affect. In the core GRN, there were 32 nodes and 42 edges. Among them, nine interactions have been supported by previous experiments. In particular, 17 additional experimentally-supported interactions can be inferred from the core GRN indirectly (the list can be found in Additional File 3). The core GRN is illustrated in Figures 3 and 5, and the adjacent list of core GRN can be found in Additional File 4.

Bottom Line: However, with the development of high-throughput technologies it is possible to gain a systematic view of biological systems to enhance the understanding of the roles of genes associated with HCC.We found that microRNAs mainly control biological functions related to mitochondria and oxidative reduction, while transcription factors control immune responses, extracellular activity and the cell cycle.In particular, we highlight the importance of the core gene regulatory network; we propose that it is highly related to HCC and we believe further experimental validation is worthwhile.

View Article: PubMed Central - HTML - PubMed

Affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, China.

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and the mechanisms that lead to the disease are still relatively unclear. However, with the development of high-throughput technologies it is possible to gain a systematic view of biological systems to enhance the understanding of the roles of genes associated with HCC. Thus, analysis of the mechanism of molecule interactions in the context of gene regulatory networks can reveal specific sub-networks that lead to the development of HCC.

Results: In this study, we aimed to identify the most important gene regulations that are dysfunctional in HCC generation. Our method for constructing gene regulatory network is based on predicted target interactions, experimentally-supported interactions, and co-expression model. Regulators in the network included both transcription factors and microRNAs to provide a complete view of gene regulation. Analysis of gene regulatory network revealed that gene regulation in HCC is highly modular, in which different sets of regulators take charge of specific biological processes. We found that microRNAs mainly control biological functions related to mitochondria and oxidative reduction, while transcription factors control immune responses, extracellular activity and the cell cycle. On the higher level of gene regulation, there exists a core network that organizes regulations between different modules and maintains the robustness of the whole network. There is direct experimental evidence for most of the regulators in the core gene regulatory network relating to HCC. We infer it is the central controller of gene regulation. Finally, we explored the influence of the core gene regulatory network on biological pathways.

Conclusions: Our analysis provides insights into the mechanism of transcriptional and post-transcriptional control in HCC. In particular, we highlight the importance of the core gene regulatory network; we propose that it is highly related to HCC and we believe further experimental validation is worthwhile.

Show MeSH
Related in: MedlinePlus