Integrated single-cell and functional analyses define fatty acid oxidation activation associates with poor prognosis in oral squamous cell carcinoma

Abstract Fatty acid oxidation (FAO) activation was reported to promote tumor progression, yet its role in oral squamous cell carcinoma (OSCC) remains incompletely understood. Here, we found that FAO was significantly activated in both OSCC tissue biopsies and OSCC cell lines. Public single-cell RNA sequencing revealed FAO activity was remarkably heterogeneous across distinct cell populations within the tumor microenvironment of OSCC. FAO-high cells laid a greater emphasis on energetic metabolism, whereas FAO-low cells showed activated immune responses. Furthermore, an effective FAO-based prognostic model was established via leveraging 101 machine learning algorithms on 4 different patient cohorts, which suggested high-FAO activity closely correlated with poor outcomes. Finally, experimental validation supported pharmacological inhibition of FAO aggravated mitochondrial energy metabolism dysfunction and promoted apoptosis of OSCC cell lines. Our findings provide novel insights into the function of FAO in OSCC and offer a potential therapeutic strategy for retarding OSCC progression.