Impact of Epigenetic Alterations in the Development of Oral Diseases

Abstract

Background: Epigenetic mechanisms alter gene expression and regulate vital cellular processes that contribute to the onset and the progression of major dental diseases. Their reversible character may prove beneficial for therapeutic targeting. This review aims to provide an update on the main epigenetic changes that contribute to the pathogenesis of Oral Squamous Cell Carcinoma (OSCC), pulpitis and periodontitis as well as in dental caries and congenital orofacial malformations, in an effort to identify potential therapeutic targets. Methods: We undertook a structured search of bibliographic databases (PubMed and MEDLINE) for peer-reviewed epigenetic research studies focused in oral diseases the last ten years. A qualitative content analysis was performed in screened papers and a critical discussion of main findings is provided. Results: Several epigenetic modifications have been associated with OSCC pathogenesis including promoter methylation of genes involved in DNA repair, cell cycle regulation and proliferation leading to malignant transformation. Additionally, epigenetic inactivation of tumor suppressor genes, overexpression of histone chaperones and several microRNAs are implicated in OSCC aggressiveness. Changes in the methylation patterns of IFN-γ and trimethylation of histone Η3Κ27 have been detected in pulpitis, along with aberrant expression of several microRNAs, mainly affecting cytokine production. Chronic periodontal disease has been associated with modifications in the methylation patterns of Toll-Like Receptor 2, Prostaglandin synthase 2, E-cadherin and some inflammatory cytokines, along with overexpression of miR-146a and miR155. Furthermore, DNA methylation was found to regulate amelogenesis and has been implicated in the pathogenesis of dental caries as well as in several congenital orofacial malformations. Conclusion: Strong evidence indicates that epigenetic changes participate in the pathogenesis of oral diseases and epigenetic targeting may be considered as a complementary therapeutic scheme to current management of oral health.

Detecting Early-Stage Oral Cancer from Clinically Diagnosed Oral Potentially Malignant Disorders by DNA Methylation Profile

“…The multistage carcinogenesis theory is also supported in oral cancer; however, specific genetic changes have not been elucidated. Epigenetic changes are commonly observed in OSCC, particularly aberrant methylation of tumor suppressor genes, which are implicated in carcinogenesis [ 19 , 20 ]. Previously, saliva, gargle fluid, and oral brushing have been examined as tools for the early detection of oral cancer using methylation as an indicator [ 21 , 22 , 23 , 24 , 25 , 26 ].…”

Differential OAT methylation correlates with cell infiltration in tumor microenvironment and overall survival postradiotherapy in oral squamous cell carcinoma patient

“…DNA methylation alteration, involved in tumor progression and readily detectable in the plasma or serum, 5 is believed as an important and early disease‐defining feature in many cancers, suggesting its potential for evaluating treating outcome 6 . For instance, promoter methylation involved in DNA repair, cell cycle regulation, and proliferation leading to malignant transformation has been reported to associate with OSCC pathogenesis 7 . A consensus has been achieved that altered DNA methylation in epithelial cells can initiate malignancy 6 .…”

MiR-148a-3p Regulates Stem Cell Osteogenic Differentiation and Enamel Development by Targeting Runt-Related Transcription Factor 2 and E-cadherin <i>via</i> the Wnt1/β-catenin Signaling Pathway

“…MiR-148a-3p is one of the widely-studied miRNAs in recent years, and it is an important player in such physiological and pathological processes as inflammation, bone formation and tumorigenesis. Disorders of miR-148a-3p can be found in multiple tumors, such as pancreatic cancer, gastric cancer, non-small cell lung cancer, breast cancer and nasopharyngeal cancer 8) . MiR-148a-3p suppresses the metastasis and invasion of gastric cancer through inhibiting the expression of DNA methylase I.…”