YTHDF2 promotes the metastasis of oral squamous cell carcinoma through the JAK-STAT pathway

RNA-binding proteins act as crucial mediators between N6-methyladenosine (m6A) modification and RNA function, playing a significant role in the recurrence and metastasis of oral squamous cell carcinoma (OSCC). YTHDF2, the first identified RNA-binding protein, has been shown to be closely associated with the prognosis of certain types of cancer. However, the role of YTHDF2 in OSCC and its underlying molecular mechanisms remain poorly understood and require further investigation. First, we analysed the expression levels of YTHDF2 and examined its correlation with clinical features using public databases and OSCC patient samples. Subsequently, a series of in vitro functional experiments were conducted to assess the effects of YTHDF2 on the proliferation, migration, and invasion capabilities of OSCC cells. Additionally, RNA-seq analysis was utilized to investigate the signalling pathways modulated by YTHDF2, which was further supported by experimental validation. Our findings revealed that YTHDF2 expression was significantly elevated in OSCC tissues and cells, with levels closely correlated with the clinical stage, pathological grade, and survival time of patients. The knockdown of YTHDF2 resulted in a significant reduction in the proliferation, migration, and invasion abilities of OSCC 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 OSCC cells. Our study demonstrated that YTHDF2 promotes the proliferation, metastasis, and invasion of OSCC by positively regulating the JAK-STAT signalling pathway, suggesting that YTHDF2 could serve as a potential prognostic marker for the diagnosis and treatment of OSCC.