Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis

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 di...

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Main Authors: Vanessa M. López-Ozuna, Ishita Gupta, Ryan Liu Chen Kiow, Emad Matanes, Hadeel Kheraldine, Amber Yasmeen, Ashraf Khalil, Semir Vranic, Ala-Eddin Al Moustafa, Halema F Al Farsi
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Toxics
Subjects:
Online Access:https://www.mdpi.com/2305-6304/8/3/73
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author Vanessa M. López-Ozuna
Ishita Gupta
Ryan Liu Chen Kiow
Emad Matanes
Hadeel Kheraldine
Amber Yasmeen
Ashraf Khalil
Semir Vranic
Ala-Eddin Al Moustafa
Halema F Al Farsi
author_facet Vanessa M. López-Ozuna
Ishita Gupta
Ryan Liu Chen Kiow
Emad Matanes
Hadeel Kheraldine
Amber Yasmeen
Ashraf Khalil
Semir Vranic
Ala-Eddin Al Moustafa
Halema F Al Farsi
author_sort Vanessa M. López-Ozuna
collection DOAJ
description 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.
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spelling doaj.art-5f51cb5542424118b1859fd45193a67a2023-11-20T14:09:38ZengMDPI AGToxics2305-63042020-09-01837310.3390/toxics8030073Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and PrognosisVanessa M. López-Ozuna0Ishita Gupta1Ryan Liu Chen Kiow2Emad Matanes3Hadeel Kheraldine4Amber Yasmeen5Ashraf Khalil6Semir Vranic7Ala-Eddin Al Moustafa8Halema F Al Farsi9Segal Cancer Center, Lady Davis Institute of Medical Research, JGH, McGill University, Montreal, QC H3T IE2, CanadaCollege of Medicine, QU Health, Qatar University, Doha PO Box 2713, QatarSegal Cancer Center, Lady Davis Institute of Medical Research, JGH, McGill University, Montreal, QC H3T IE2, CanadaSegal Cancer Center, Lady Davis Institute of Medical Research, JGH, McGill University, Montreal, QC H3T IE2, CanadaCollege of Medicine, QU Health, Qatar University, Doha PO Box 2713, QatarSegal Cancer Center, Lady Davis Institute of Medical Research, JGH, McGill University, Montreal, QC H3T IE2, CanadaCollege of Pharmacy, QU Health, Qatar University, Doha PO Box 2713, QatarCollege of Medicine, QU Health, Qatar University, Doha PO Box 2713, QatarCollege of Medicine, QU Health, Qatar University, Doha PO Box 2713, QatarCollege of Medicine, QU Health, Qatar University, Doha PO Box 2713, QatarWater-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.https://www.mdpi.com/2305-6304/8/3/73smokewater pipehead and neck cancersgene dysregulationoral epithelial cells
spellingShingle Vanessa M. López-Ozuna
Ishita Gupta
Ryan Liu Chen Kiow
Emad Matanes
Hadeel Kheraldine
Amber Yasmeen
Ashraf Khalil
Semir Vranic
Ala-Eddin Al Moustafa
Halema F Al Farsi
Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis
Toxics
smoke
water pipe
head and neck cancers
gene dysregulation
oral epithelial cells
title Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis
title_full Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis
title_fullStr Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis
title_full_unstemmed Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis
title_short Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis
title_sort water pipe smoking exposure deregulates a set of genes associated with human head and neck cancer development and prognosis
topic smoke
water pipe
head and neck cancers
gene dysregulation
oral epithelial cells
url https://www.mdpi.com/2305-6304/8/3/73
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