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Published on: March 3, 2015
Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN
Chunyu Pan1,2,3, Yuyan Zhu2,4, Meng Yu5
1Northeastern University, Shenyang, China.
Background:
MYCN is an oncogenic transcription factor of the MYC family and plays an important role in the formation of tissues and organs during development before birth. Due to the difficulty in drugging MYCN directly, revealing the molecules in MYCN regulatory networks will help to identify effective therapeutic targets.
Methods:
We utilized network controllability theory, a recent developed powerful tool, to identify the potential drug target around MYCN based on Protein-Protein interaction network of MYCN. First, we constructed a Protein-Protein interaction network of MYCN based on public databases. Second, network control analysis was applied on network to identify driver genes and indispensable genes of the MYCN regulatory network. Finally, we developed a novel integrated approach to identify potential drug targets for regulating the function of the MYCN regulatory network.
Results:
We constructed an MYCN regulatory network that has 79 genes and 129 interactions. Based on network controllability theory, we analyzed driver genes which capable to fully control the network. We found 10 indispensable genes whose alternation will significantly change the regulatory pathways of the MYCN network. We evaluated the stability and correlation analysis of these genes and found EGFR may be the potential drug target which closely associated with MYCN.
Conclusion:
Together, our findings indicate that EGFR plays an important role in the regulatory network and pathways of MYCN and therefore may represent an attractive therapeutic target for cancer treatment.
Insights
Identifying potential drug targets for MYCN regulation is crucial. Network controllability theory revealed 10 indispensable genes, with EGFR emerging as a promising therapeutic target for MYCN-associated cancers.
Area of Science:
- Oncology
- Systems Biology
- Bioinformatics
Background:
- MYCN is a key oncogenic transcription factor vital for embryonic development.
- Directly targeting MYCN is challenging, necessitating identification of regulatory network components.
- Understanding MYCN's regulatory network is essential for discovering novel therapeutic strategies.
Purpose of the Study:
- To identify potential drug targets within the MYCN regulatory network.
- To leverage network controllability theory for target identification.
- To find molecules that can effectively regulate MYCN's function.
Main Methods:
- Construction of a MYCN-centric Protein-Protein Interaction (PPI) network using public databases.
- Application of network controllability theory to identify driver and indispensable genes.
- Development of an integrated approach for potential drug target identification.
Main Results:
- A MYCN regulatory network comprising 79 genes and 129 interactions was established.
- Network controllability analysis identified 10 indispensable genes significantly impacting MYCN network pathways.
- Epidermal Growth Factor Receptor (EGFR) was identified as a potential drug target due to its association with MYCN.
Conclusions:
- EGFR plays a significant role in the MYCN regulatory network and pathways.
- EGFR represents a potential therapeutic target for cancers involving MYCN.
- This study highlights the utility of network controllability theory in identifying cancer drug targets.
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