Abstract
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.
Highlights
Cancer is one of the major non-communicable diseases [1] and is accountable for millions of deaths per year worldwide
According to the World Health Organization (WHO), there are mainly three reasons that lead to these aberrations, with tobacco consumption heading the list, which is single-handedly responsible for around 22% of deaths by cancer globally [4]
A NNK rewired protein–protein interaction network (PPIN), with the help of various systems biology tools, was explored for the identification of potential targets involved in tobacco induced cancer development
Summary
Cancer is one of the major non-communicable diseases [1] and is accountable for millions of deaths per year worldwide. According to the World Health Organization (WHO), cancer is the second major cause of morbidity, with an estimate of 9.6 billion deaths in 2018 [2]. Cancer is a multistage process caused by aberrations in the cellular processes. Cancer is caused by mutation in any single gene and by the accumulation of mutations in multiple genes, a phenomenon described as ‘oncogene addiction’ [3]. According to the WHO, there are mainly three reasons that lead to these aberrations, with tobacco consumption heading the list, which is single-handedly responsible for around 22% of deaths by cancer globally [4]. We have immense information on how tobacco consumption has direct implications in cancer, specially lung, head and neck, stomach, liver, and pancreatic cancers [5,6]
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