A Systemic and Integrated Analysis of p63-Driven Regulatory Networks in Mouse Oral Squamous Cell Carcinoma

ABSTRACT: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and despite therapeutic advances, late-stage diagnoses continue to negatively affect survival, presenting a continuing challenge for clinicians. Detailed molecular characterization by recent bulk and single-cell RNA-sequencing datasets from OSCC suggest that identification of prognostic biomarkers may lead to more targeted therapies, improving  patient outcomes. Development of OSCC is associated with exposure to tobacco, alcohol consumption, and infection with human papillomavirus. The mouse model of 4-Nitroquinoline 1-oxide (4NQO) carcinogenesis produces a spectrum of neoplastic lesions that are a robust model of tobacco-induced OSCC. Specifically, studies have shown that similar to human OSCC, mouse OSCC shows upregulation of the oncogenic master transcription factor p63. We performed complementary loss- and gain-of-function experiments of p63 in mouse 4NQO-transformed OSCC cell lines and utilized RNA-sequencing and ChIP-sequencing to uncover the p63 oncogenic network. By combining our signature with publicly available bulk and scRNA-seq data, we generated a murine p63 signature that we have utilized to better understand the role of p63 in mOSCC. Our analyses have identified several potential biomarkers and conserved pathways that are relevant to hOSCC, as well as highlighted the dynamic role of p63 in migration and invasion.

ORGANISM(S): Mus musculus

PROVIDER: GSE217669 | GEO | 2023/01/10

REPOSITORIES: GEO