Systems biology holds importance as it helps in getting a holistic view of the connections of biomolecules. Systems biology is an interdisciplinary field, which is a combination of mathematics, computer science, and biology. In this study, attempts have been made to exploit the system biology approach for an investigation of the overall impact of tobacco-generated carcinogen NNK on molecular systems. Earlier studies have shown that NNK has significant impact on steatohepatitis, Alzheimer’s disease, and tuberculosis, for example. NNK is not just responsible for causing cancer but also holds serious implications in other diseases as well. NNK and its derivative, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), binds with the DNA and forms DNA adducts, the resultant of which may lead to genetic mutations followed by the deregulation of normal cellular processes. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the main components in tobacco that plays a major role in the causation of cancer. Ĭurrently, we have immense information on how tobacco consumption has direct implications in cancer, specially lung, head and neck, stomach, liver, and pancreatic cancers. 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. Cancer is not only caused by mutation in any single gene but also by the accumulation of mutations in multiple genes, a phenomenon described as ‘oncogene addiction’. Cancer is a multistage process caused by aberrations in the cellular processes. 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. GO enrichment analysis revealed that mostly cell cycle regulatory proteins were affected by NNK.Ĭancer is one of the major non-communicable diseases and is accountable for millions of deaths per year worldwide. Further, scrutiny of the targeted biomolecules was done by the graph theory and molecular docking. For the modulation, Molecular COmplex DEtection (MCODE) was used to generate 19 modules containing 115 seed proteins. Gene ontology (GO) enrichment was performed on the seed proteins extracted from various modules to find the most affected pathways by the genes/proteins. The noise was removed from PPIN by the method of modulation. 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. 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. Despite these studies, a clear molecular mechanism and the impact of NNK on various system-level networks is not known. However, it is strongly linked with cancer development.
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A plethora of studies have been conducted in the past aiming to decipher the association of NNK with other diseases.
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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). Cancer is the second deadliest disease listed by the WHO.