YTHDF2 Promotes the Metastasis of Oral Squamous Cell Carcinoma through the JAK- STAT Pathway

Background: RNA-binding proteins act as crucial mediators between m6A modification and RNA function, playing a significant role in the recurrence and metastasis of oral squamous cell carcinoma. YTHDF2, the first identified RNA-binding protein, is associated with the prognosis of certain cancer patients. However, the role of YTHDF2 in oral squamous cell carcinoma and its underlying molecular mechanism have not been fully explored. Methods: First, we analysed the expression levels of YTHDF2 and itscorrelation with clinical features via the use of public databases and oral squamous cell carcinoma patient samples. Subsequently, in vitro functional experiments were conducted to assess the effects of YTHDF2 on the proliferation, migration and invasion capabilities of oral squamous cell carcinoma cells. Additionally, RNA-seq analysis was utilized to investigate the signalling pathways modulated by YTHDF2, followed by experimental validation. Results: Our findings revealed that YTHDF2 expression was significantly elevated in oral squamous cell carcinoma tissues and cells, with levels significantly correlated with the clinical stage, pathological grade, and survival time of patients. The knockdown of YTHDF2 resulted in decreased proliferation, migration and invasion abilities in oral squamous cell carcinoma cells. Furthermore, RNA sequencing data indicated that silencing YTHDF2 suppressed the JAK-STAT signalling pathway, and the use of STAT3 activators reversed this suppressive effect in oral squamous cell carcinoma cells. Conclusion: Our study demonstrated that YTHDF2 promotes the proliferation, metastasis and invasion of oral squamous cell carcinoma by positively regulating the JAK-STAT signalling pathway, suggesting that YTHDF2 could serve as a potential prognostic marker for oral squamous cell carcinoma.