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

Author(s)

Larissa Miyuki Okano ^[1] ; Lívia Maria Maciel da Fonseca ^[2] ; Isabela Dias Erthal ^[3] ; Tathiane Maistro Malta ^[4]

Affiliation

^[1] Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto - Brasil

^[2] Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Brasil

^[3] Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto - Brasil

^[4] Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Brasil

• Document type: Journal article
• Source: GENETICS AND MOLECULAR BIOLOGY; v. 46, n. 2 2023-06-19.

Abstract

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. (AU)

• FAPESP's process: 21/08190-0 - Mapping epigenomic signatures associated with IDH mutation
• Grantee: Isabela Dias Erthal
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/00583-0 - Integrative epigenomic analysis of gliomas: defining regulatory regions associated with stemness and with the hypermethylator phenotype of IDH1/2 mutant tumors
• Grantee: Tathiane Maistro Malta Pereira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/14928-1 - Integrative epigenomic analysis of gliomas - defining regulatory regions associated with stemness and with the hypermethylator phenotype of IDH1/2 mutant tumors
• Grantee: Tathiane Maistro Malta Pereira
• Support Opportunities: Scholarships in Brazil - Young Researchers