Abstract
BackgroundMYCN 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.MethodsWe 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.ResultsWe 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.ConclusionTogether, 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.
Highlights
The MYC proto-oncogene family consists of three paralogs: cMYC, MYCN, and MYCL [1, 2]
The results showed that network controllability theory may provide new ideas to reveal the function of MYCN and target MCYN, which is of great importance and application prospect
Consider a Protein-Protein interactions (PPI) network, a node of the network represents a protein and the interactions between proteins are the edges of the network
Summary
The MYC proto-oncogene family consists of three paralogs: cMYC, MYCN, and MYCL [1, 2]. The MYCN cancer gene in the MYC family is a structurally and functionally similar fragment of MYC discovered by Schwab [3] in 1983. It acts to promote cell proliferation, and inhibit cell differentiation, apoptosis, or programmed cell death [4,5,6]. The problem of targeting MYCN can be translated into the study of the MYCN regulatory network of its interactions. 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
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