Effect of DAZAP1 deletion on gene expression in Cal27 cell line during progression of oral squamous cell carcinoma

Tumor invasion and metastasis are the underlying cause of clinical refractoriness in oral squamous carcinoma (OSCC). Energy metabolism reprogramming has been identified as a vital process mediating tumor metastasis, indicating an urgent need for in-depth investigate into the specific mechanisms of tumor energy metabolism. Here, we identify an RNA-binding protein, DAZ associate protein 1 (DAZAP1), as a tumor-promoting factor to play an important role in OSCC progression. In vitro assays demonstrated that DAZAP1 was significantly upregulated in OSCC, while enhanced the migration and invasion of OSCC cells as well as epithelial-mesenchymal transition (EMT). RNA-seq analysis and experimental validation showed that DAZAP1 can regulate mitochondrial energy metabolism in OSCC. Mechanistically, we found that DAZAP1 underwent liquid-liquid phase separation (LLPS) to accumulate in the nucleus and enhanced cytochrome-c oxidase 16 (COX16) expression via regulating pre-mRNA alternative splicing, thereby promoted OSCC invasion and mitochondrial respiration. Finally, we observed a significant positive correlation between DAZAP1 and COX16, and high expression of these two proteins were both closely associated with poor prognosis in OSCC patients. Together, our study reveals a novel regulatory mechanism of DAZPA1 in mitochondrial metabolism and tumor development of OSCC by phase separation, suggesting the potential role of DAZAP1 in developing therapeutic strategies against OSCC invasion and metastasis.