Abstract
Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are still unknown. In this study, human normal oral epithelial (HNOE) cells, NanoString PanCancer Pathways panel of 770 gene transcripts and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were applied to discover differentially expressed genes (DEG) modulated by WPS. In silico analysis was performed to analyze the impact of these genes in HN cancer patient’s biology and outcome. We found that WPS can induce the epithelial–mesenchymal transition (EMT: hallmark of cancer progression) of HNOE cells. More significantly, our analysis of NanoString revealed 23 genes deregulated under the effect of WPS, responsible for the modulation of cell cycle, proliferation, migration/invasion, apoptosis, signal transduction, and inflammatory response. Further analysis was performed using qRT-PCR of HNOE WPS-exposed and unexposed cells supported the reliability of our NanoString data. Moreover, we demonstrate those DEG to be upregulated in cancer compared with normal tissue. Using the Kaplan–Meier analysis, we observed a significant association between WPS-deregulated genes and relapse-free survival/overall survival in HN cancer patients. Our findings imply that WPS can modulate EMT as well as a set of genes that are directly involved in human HN carcinogenesis, thereby affecting HN cancer patients’ survival.
Highlights
Tobacco smoking is the most common preventable risk factor for several non-communicable diseases, such as, cardiovascular, lung, diabetes as well as cancer, and can be considered lethal [1,2].Widespread tobacco consumption is somewhat attributed to the variation in available consumption methods, such as cigarettes, electronic cigarettes (E-cigarettes), cigars, and water-pipe smokingToxics 2020, 8, 73; doi:10.3390/toxics8030073 www.mdpi.com/journal/toxics (WPS)
In order to study the effect of Water-pipe smoking (WPS) on human head and neck (HN) carcinogenesis, we examined the outcome of WPS on two human normal oral epithelial, 2N and 11N, which were established in our lab [28]
We found that WPS exposure induces5EMT, Toxics
Summary
Tobacco smoking is the most common preventable risk factor for several non-communicable diseases, such as, cardiovascular, lung, diabetes as well as cancer, and can be considered lethal [1,2].Widespread tobacco consumption is somewhat attributed to the variation in available consumption methods, such as cigarettes, electronic cigarettes (E-cigarettes), cigars, and water-pipe smokingToxics 2020, 8, 73; doi:10.3390/toxics8030073 www.mdpi.com/journal/toxics (WPS). Tobacco smoking is the most common preventable risk factor for several non-communicable diseases, such as, cardiovascular, lung, diabetes as well as cancer, and can be considered lethal [1,2]. Global trend of tobacco smoking has started to shift towards WPS in addition to. Global increase in WPS use is due to several factors including its availability in several delectable flavors and aromas along with its association with socializing, relaxation, and entertainment. Additional motives include peer-pressure, low-cost, fashion, and inquisitiveness [3,8]. People from the Middle East and those of Middle Eastern descent in Western countries smoke WPS, as they consider it to be a part of their culture, giving rise to this trend in the Western world [9]
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