Epigenomic integrative analysis pinpoint master regulator transcription factors associated with tumorigenesis in squamous cell carcinoma of oral tongue

Abstract

Head and Neck Cancer (HNC) is a heterogeneous group of cancers, which includes cancers arising in the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx. Epidemiological studies have revealed that several factors such as tobacco and alcohol use, exposure to environmental pollutants, viral infection, and genetic factors are risk factors for developing HNC. The squamous cell carcinoma of oral tongue (SCCOT), which is significantly more aggressive than the other forms of oral squamous cell carcinoma, presents a propensity for rapid local invasion and spread, and a high recurrence rate. Dysregulation in the epigenetic machinery of cancer cells might help uncover the mechanisms of SCOOT tumorigenesis. Here, we used DNA methylation changes to identify cancer-specific enhancers that were enriched for specific transcription factor binding sites (TFBS), and potential master regulator transcription factors (MRTF) associated with SCCOT. We identified the activation of MRTFs associated with increased invasiveness, metastasis, epithelial-to-mesenchymal transition, poor prognosis, and stemness. On the other hand, we found the downregulation of MRTFs associated with tumor suppression. The identified MRTFs should be further investigated to clarify their role in oral cancer tumorigenesis and for their potential use as biological markers.