RANBP1 promotes oral cancer progression through activating YAP1 and NDUFB3 derived from the database of single-cell...

Oral cavity squamous cell carcinoma (OSCC) is the most common head and neck cancer, thriving in microenvironments composed of cancer cells, stromal tissue, and extracellular matrix. Extensive local invasion and cervical nodal metastasis can lead to poor treatment outcomes for OSCC. We created a single-cell transcriptomic database of OSCC using biopsies from 10 individuals to identify candidate genes. Ran-specific binding protein 1 (RANBP1) was identified as a gene with differential expression between malignant and normal epithelial cells. Analysis of the Cancer Genome Atlas Program (TCGA) OSCC and Taiwanese cohorts confirmed that higher RANBP1 levels are significantly associated with worse prognosis. Functional tests showed that knocking down RANBP1 reduced cell proliferation and invasion by decreasing proteins involved in focal adhesion, invadopodia formation, and epithelial-mesenchymal transition. Inhibiting RANBP1 also decreased vascular spread in zebrafish tumor xenografts, while overexpressing RANBP1 had the opposite effect. The overexpression of RANBP1 significantly increased tumor growth in NOD/SCID xenografts. RANBP1 was positively correlated with the oxidative phosphorylation pathway. Cells with reduced RANBP1 showed lower levels of NADH ubiquinone oxidoreductase subunit B3 (NDUFB3) and had impaired mitochondrial function. Additionally, RANBP1 depletion decreased activation of Yes1 associated transcriptional regulator (YAP1). Increased NDUFB3 expression in RANBP1-overexpressing cells was reversed by YAP1 inhibitor verteporfin treatment or knocking down YAP1. RANBP1 enhances a more invasive microenvironment of OSCC.