Epigenetic mechanisms in oral carcinogenesis

Abstract

Dysregulation of gene expression is a frequent occurrence in oral squamous cell carcinoma (OSCC). However, accumulating evidence suggests that in contrast to genetics, epigenetic modifications consisting of aberrant DNA methylation, histone modifications and altered expression of miRNAs induce OSCC tumorigenesis and perhaps play a more central role in the evolution and progression of this disease. The unifying theme among these three epigenetic mechanisms remains the same, which is aberrant regulation of gene expression. In this article, we provide a comprehensive review of the impact of epigenetics on oral tumorigenesis with a systematic report on aberrant DNA methylation, histone modifications and miRNA regulation in the pathogenesis of OSCC. We provide insights into recent studies on the prospect of biomarkers for early detection and indication of disease recurrence, and novel treatment modalities.

Figure 1. Progression of oral squamous cell carcinoma

While oral squamous cell carcinoma progresses from one stage to the next, the oral tissue is marked by distinct molecular alterations during each step. Risk factors for oral cancers, such as alcohol consumption or tobacco abuse, lead to a series of genetic and epigenetic alterations in the oral tissues, which eventually may progress to advanced oral cancer. This figure highlights some of the specific genetic and aberrant methylation alterations that occur during oral squamous cell carcinoma progression.

Figure 2. Role of miRNAs in the development and progression of oral squamous cell carcinoma

Two important epigenetic mechanisms support OSCC tumorigenesis: overexpression of oncogenic miRNAs (or oncoMiRs) and underexpression of tumor suppressor miRNAs (or tsMiRs). Listed in this figure are some of the most important miRNAs and their gene targets that have emerged as key regulators of gene expression in oral cancer. OSCC: Oral squamous cell carcinoma.