Investigation of Precise Molecular Mechanistic Action of Tobacco-Associated Carcinogen `NNK´ Induced Carcinogenesis: A System Biology Approach.
NNK
cancer
gene ontology.
protein–protein interaction network
systems biology
topological analysis
Journal
Genes
ISSN: 2073-4425
Titre abrégé: Genes (Basel)
Pays: Switzerland
ID NLM: 101551097
Informations de publication
Date de publication:
26 07 2019
26 07 2019
Historique:
received:
14
06
2019
revised:
22
07
2019
accepted:
24
07
2019
entrez:
31
7
2019
pubmed:
31
7
2019
medline:
10
1
2020
Statut:
epublish
Résumé
Cancer is the second deadliest disease listed by the WHO. One of the major causes of cancer disease is tobacco and consumption possibly due to its main component, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A plethora of studies have been conducted in the past aiming to decipher the association of NNK with other diseases. However, it is strongly linked with cancer development. Despite these studies, a clear molecular mechanism and the impact of NNK on various system-level networks is not known. In the present study, system biology tools were employed to understand the key regulatory mechanisms and the perturbations that will happen in the cellular processes due to NNK. To investigate the system level influence of the carcinogen, NNK rewired protein-protein interaction network (PPIN) was generated from 544 reported proteins drawn out from 1317 articles retrieved from PubMed. The noise was removed from PPIN by the method of modulation. Gene ontology (GO) enrichment was performed on the seed proteins extracted from various modules to find the most affected pathways by the genes/proteins. For the modulation, Molecular COmplex DEtection (MCODE) was used to generate 19 modules containing 115 seed proteins. Further, scrutiny of the targeted biomolecules was done by the graph theory and molecular docking. GO enrichment analysis revealed that mostly cell cycle regulatory proteins were affected by NNK.
Identifiants
pubmed: 31357510
pii: genes10080564
doi: 10.3390/genes10080564
pmc: PMC6723528
pii:
doi:
Substances chimiques
Carcinogens
0
Nitrosamines
0
Proteome
0
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
7S395EDO61
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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