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Sci Rep. 2018 May 4;8(1):7040. doi: 10.1038/s41598-018-25498-2.

Cigarette smoke and chewing tobacco alter expression of different sets of miRNAs in oral keratinocytes.

Author information

1
Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India.
2
School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, 690525, India.
3
Manipal Academy of Higher Education, Manipal, 576104, India.
4
School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, 751024, India.
5
Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India.
6
Department of Surgery, UC San Diego, Moores Cancer Center, La Jolla, CA, 92093, USA.
7
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
8
Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India. harsha@ibioinformatics.org.
9
Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India. aditi@ibioinformatics.org.

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.

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