Abstract
Carcinogenic effect of tobacco in oral cancer is through chewing and/or smoking. Significant differences exist in development of oral cancer between tobacco users and non-users. However, molecular alterations induced by different forms of tobacco are yet to be fully elucidated. We developed cellular models of chronic exposure to chewing tobacco and cigarette smoke using immortalized oral keratinocytes. Chronic exposure to tobacco resulted in increased cell scattering and invasiveness in immortalized oral keratinocytes. miRNA sequencing using Illumina HiSeq 2500 resulted in the identification of 10 significantly dysregulated miRNAs (4 fold; p ≤ 0.05) in chewing tobacco treated cells and 6 in cigarette smoke exposed cells. We integrated this data with global proteomic data and identified 36 protein targets that showed inverse expression pattern in chewing tobacco treated cells and 16 protein targets that showed inverse expression in smoke exposed cells. In addition, we identified 6 novel miRNAs in chewing tobacco treated cells and 18 novel miRNAs in smoke exposed cells. Integrative analysis of dysregulated miRNAs and their targets indicates that signaling mechanisms leading to oncogenic transformation are distinct between both forms of tobacco. Our study demonstrates alterations in miRNA expression in oral cells in response to two frequently used forms of tobacco.
| Original language | English (US) |
|---|---|
| Article number | 7040 |
| Journal | Scientific Reports |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2018 |
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ASJC Scopus subject areas
- General
Cite this
Cigarette smoke and chewing tobacco alter expression of different sets of miRNAs in oral keratinocytes. / Bhat, Mohd Younis; Advani, Jayshree; Rajagopalan, Pavithra; Patel, Krishna; Nanjappa, Vishalakshi; Solanki, Hitendra S.; Patil, Arun H.; Bhat, Firdous A.; Mathur, Premendu P.; Nair, Bipin; Prasad, T. S.Keshava; Califano, Joseph A.; Sidransky, David; Gowda, Harsha; Chatterjee, Aditi.
In: Scientific Reports, Vol. 8, No. 1, 7040, 01.12.2018.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Cigarette smoke and chewing tobacco alter expression of different sets of miRNAs in oral keratinocytes
AU - Bhat, Mohd Younis
AU - Advani, Jayshree
AU - Rajagopalan, Pavithra
AU - Patel, Krishna
AU - Nanjappa, Vishalakshi
AU - Solanki, Hitendra S.
AU - Patil, Arun H.
AU - Bhat, Firdous A.
AU - Mathur, Premendu P.
AU - Nair, Bipin
AU - Prasad, T. S.Keshava
AU - Califano, Joseph A.
AU - Sidransky, David
AU - Gowda, Harsha
AU - Chatterjee, Aditi
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Carcinogenic effect of tobacco in oral cancer is through chewing and/or smoking. Significant differences exist in development of oral cancer between tobacco users and non-users. However, molecular alterations induced by different forms of tobacco are yet to be fully elucidated. We developed cellular models of chronic exposure to chewing tobacco and cigarette smoke using immortalized oral keratinocytes. Chronic exposure to tobacco resulted in increased cell scattering and invasiveness in immortalized oral keratinocytes. miRNA sequencing using Illumina HiSeq 2500 resulted in the identification of 10 significantly dysregulated miRNAs (4 fold; p ≤ 0.05) in chewing tobacco treated cells and 6 in cigarette smoke exposed cells. We integrated this data with global proteomic data and identified 36 protein targets that showed inverse expression pattern in chewing tobacco treated cells and 16 protein targets that showed inverse expression in smoke exposed cells. In addition, we identified 6 novel miRNAs in chewing tobacco treated cells and 18 novel miRNAs in smoke exposed cells. Integrative analysis of dysregulated miRNAs and their targets indicates that signaling mechanisms leading to oncogenic transformation are distinct between both forms of tobacco. Our study demonstrates alterations in miRNA expression in oral cells in response to two frequently used forms of tobacco.
AB - Carcinogenic effect of tobacco in oral cancer is through chewing and/or smoking. Significant differences exist in development of oral cancer between tobacco users and non-users. However, molecular alterations induced by different forms of tobacco are yet to be fully elucidated. We developed cellular models of chronic exposure to chewing tobacco and cigarette smoke using immortalized oral keratinocytes. Chronic exposure to tobacco resulted in increased cell scattering and invasiveness in immortalized oral keratinocytes. miRNA sequencing using Illumina HiSeq 2500 resulted in the identification of 10 significantly dysregulated miRNAs (4 fold; p ≤ 0.05) in chewing tobacco treated cells and 6 in cigarette smoke exposed cells. We integrated this data with global proteomic data and identified 36 protein targets that showed inverse expression pattern in chewing tobacco treated cells and 16 protein targets that showed inverse expression in smoke exposed cells. In addition, we identified 6 novel miRNAs in chewing tobacco treated cells and 18 novel miRNAs in smoke exposed cells. Integrative analysis of dysregulated miRNAs and their targets indicates that signaling mechanisms leading to oncogenic transformation are distinct between both forms of tobacco. Our study demonstrates alterations in miRNA expression in oral cells in response to two frequently used forms of tobacco.
UR - http://www.scopus.com/inward/record.url?scp=85046634719&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046634719&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-25498-2
DO - 10.1038/s41598-018-25498-2
M3 - Article
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 7040
ER -