Epigenetic profiling reveals key super-enhancer networks driving oncogenesis in HPV-positive HNSCC.

ABSTRACT: Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is a growing subset of cancer cases distinct from HPV-negative by fewer genetic mutations and prevalent epigenetic dysregulation. We mapped H3K27ac-marked super-enhancers (SEs) via ChIP-seq in HPV+ patient-derived xenografts (PDXs) and normal oropharyngeal mucosa, identifying tumor-specific SE domains (T-SEDs) enriched for transcription factors (TFs) including TP63, FOSL1, and JUND. These SE-associated TFs regulate key oncogenic pathways and are downregulated by BRD4 inhibition with JQ1, highlighting sensitivity to epigenetic modulation. RNA-seq data revealed coordinated dysregulation of enhancer RNAs and mRNAs near T-SEDs, linked to upregulated pathways including epithelial-mesenchymal transition and E2F ta

SUBMITTER: Zamuner FT 

PROVIDER: S-EPMC12664489 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature