Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review

Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent and significant type of oral cancer that has far-reaching health implications worldwide. Epigenetics, a field focused on studying heritable changes in gene expression without modifying DNA sequence, plays a pivotal role in OSCC. Epigenetic changes, encompassing DNA methylation, histone modifications, and miRNAs, exert control over gene activity and cellular characteristics. In OSCC, aberrant DNA methylation of tumor suppressor genes (TSG) leads to their inactivation, subsequently facilitating tumor growth. As a result, distinct patterns of gene methylation hold promise as valuable biomarkers for the detection of OSCC. Oral cancer treatment typically involves surgery, radiation therapy, and chemotherapy, but even with these treatments, cancer cells cannot be effectively targeted and destroyed. Researchers are therefore exploring new methods to target and eliminate cancer cells. One promising approach is the use of epigenetic modifiers, such as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors, which have been shown to modify abnormal epigenetic patterns in OSCC cells, leading to the reactivation of TSGs and the suppression of oncogenes. As a result, epigenetic-targeted therapies have the potential to directly alter gene expression and minimize side effects. Several studies have explored the efficacy of such therapies in the treatment of OSCC. Although studies have investigated the efficacy of epigenetic therapies, challenges in identifying reliable biomarkers and developing effective combination treatments are acknowledged. Of note, epigenetic mechanisms play a significant role in drug resistance in OSCC and other cancers. Aberrant DNA methylation can silence tumor suppressor genes, while alterations in histone modifications and chromatin remodeling affect gene expression related to drug metabolism and cell survival. Thus, understanding and targeting these epigenetic processes offer potential strategies to overcome drug resistance and improve the efficacy of cancer treatments in OSCC. This comprehensive review focuses on the complex interplay between epigenetic alterations and OSCC cells. This will involve a deep dive into the mechanisms underlying epigenetic modifications and their impact on OSCC, including its initiation, progression, and metastasis. Furthermore, this review will present the role of epigenetics in the treatment and diagnosis of OSCC.

Identification of Stage-Specific microRNAs That Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Genetics and Epigenetics

“…MiRNAs, a class of crucial epigenetic regulators of gene expression, have emerged as key players in precision oncology, serving as ideal biomarkers for liquid biopsy, since they exhibit strong diagnostic potential by reflecting a tissue's malignant state through the quantification of their expressional dysregulation [3,8,9,12,16]. In recent years, the expression of numerous miRNAs has been studied in OSCC, resulting in a vast number of experimental data with at least 256 molecules reported to be either upregulated or downregulated in OSCC derived-samples (tissue, saliva or blood) [6,8,9,[17][18][19][20][21][22][23][24][25][26][27][28], while the majority exhibits similar dysregulation in other neoplasms as well. Consequently, there is a state of disarray regarding the interpretation of findings and the identification of the most representative molecules for the disease at large, but particularly for its early asymptomatic stages [8].…”