Epigenetic alterations in oral cancer: Tobacco as the prime culprit

¹ Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, India- 201309
^1* Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, India-201309 This email address is being protected from spambots. You need JavaScript enabled to view it. , shalim.mam@,jiitac.in

Abstract

Oral squamous cell carcinoma accounts for about 90% of the cases of oral cancer. It also remains the major contributor to cancer-related deaths worldwide. Tobacco use is a major cause, comprising more than 60 harmful chemicals that can cause cellular and molecular damage. Recent evidence indicates the induction of carcinogenic effects by tobacco via epigenetic and genetic alterations. This includes DNA methylation, histone modifications, and abnormally regulated miRNA expression. The overall disruption of these mechanisms causes further downregulation of tumor suppressor genes and activation of oncogenes. Histone-modifying enzymes and DNA methyltransferases are some essential enzymes in this process that link tobacco exposure to changes in chromatin structure and gene silencing. Additionally, these epigenetic modifications induced by tobacco and its derivatives possess the potential to serve as biomarkers for early diagnosis, prognostic prediction, and therapeutic stratification. Novel therapeutic avenues like DNA Methyltransferase and Histone deacetylase inhibitors are emerging as epigenetic modification therapies. These exhibit the ability to reverse these abnormal modifications by restoring the normal gene functioning. This comprehensive review brings together the current understanding of altered epigenetics by tobacco consumption and how important epigenetic biomarkers and epi-drugs are in fighting treatment resistance. Comprehending this interaction not only yields mechanistic insights but also facilitates translational opportunities for targeted therapy in oral carcinoma.