TY - JOUR
T1 - Investigation of precise molecular mechanistic action of tobacco-associated carcinogen `NNK´ induced carcinogenesis
T2 - A system biology approach
AU - Anukriti,
AU - Dhasmana, Anupam
AU - Uniyal, Swati
AU - Somvanshi, Pallavi
AU - Bhardwaj, Uma
AU - Gupta, Meenu
AU - Haque, Shafiul
AU - Lohani, Mohtashim
AU - Kumar, Dhruv
AU - Ruokolainen, Janne
AU - Kesari, Kavindra Kumar
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
KW - Cancer
KW - Gene ontology
KW - NNK
KW - Protein
KW - Protein interaction network
KW - Systems biology
KW - Topological analysis
UR - http://www.scopus.com/inward/record.url?scp=85070642203&partnerID=8YFLogxK
U2 - 10.3390/genes10080564
DO - 10.3390/genes10080564
M3 - Article
AN - SCOPUS:85070642203
SN - 2073-4425
VL - 10
SP - 1
EP - 22
JO - Genes
JF - Genes
IS - 8
M1 - 564
ER -
