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Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN

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 effec...

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Autores principales: Pan, Chunyu, Zhu, Yuyan, Yu, Meng, Zhao, Yongkang, Zhang, Changsheng, Zhang, Xizhe, Yao, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096904/
https://www.ncbi.nlm.nih.gov/pubmed/33968733
http://dx.doi.org/10.3389/fonc.2021.633579
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author Pan, Chunyu
Zhu, Yuyan
Yu, Meng
Zhao, Yongkang
Zhang, Changsheng
Zhang, Xizhe
Yao, Yang
author_facet Pan, Chunyu
Zhu, Yuyan
Yu, Meng
Zhao, Yongkang
Zhang, Changsheng
Zhang, Xizhe
Yao, Yang
author_sort Pan, Chunyu
collection PubMed
description 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.
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spelling pubmed-80969042021-05-06 Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN Pan, Chunyu Zhu, Yuyan Yu, Meng Zhao, Yongkang Zhang, Changsheng Zhang, Xizhe Yao, Yang Front Oncol Oncology 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. Frontiers Media S.A. 2021-04-21 /pmc/articles/PMC8096904/ /pubmed/33968733 http://dx.doi.org/10.3389/fonc.2021.633579 Text en Copyright © 2021 Pan, Zhu, Yu, Zhao, Zhang, Zhang and Yao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Pan, Chunyu
Zhu, Yuyan
Yu, Meng
Zhao, Yongkang
Zhang, Changsheng
Zhang, Xizhe
Yao, Yang
Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN
title Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN
title_full Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN
title_fullStr Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN
title_full_unstemmed Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN
title_short Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN
title_sort control analysis of protein-protein interaction network reveals potential regulatory targets for mycn
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096904/
https://www.ncbi.nlm.nih.gov/pubmed/33968733
http://dx.doi.org/10.3389/fonc.2021.633579
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