YTHDF1 promotes radioresistance in nasopharyngeal carcinoma through the SATB1/Wnt/β-catenin pathway

Radiotherapy resistance is a major cause of treatment failure in nasopharyngeal carcinoma (NPC). Elucidating the mechanisms underlying NPC radiotherapy resistance holds great importance for optimizing NPC treatment strategies. In this study, a radiotherapy-resistant NPC cell model (CNE-2R) was established using graded ionizing radiation (IR). Abnormally high expression levels of YTHDF1 and SATB1 were observed in NPC cells, particularly in CNE-2R. Subsequently, we constructed CNE-2R cells with YTHDF1 knockdown (siYTHDF1) and evaluated the impact of YTHDF1 knockdown on the biological functions of CNE-2R cells through EdU assay, Transwell assay, ELISA, and flow cytometry. The results demonstrated that knockdown of YTHDF1 inhibited the proliferation, invasion, and migration abilities of CNE-2R cells, and induced cell apoptosis. Pearson correlation analysis revealed a positive correlation between YTHDF1 and SATB1 expression. Meanwhile, Western blot results indicated that knockdown of YTHDF1 reduced the expression of SATB1, Wnt1, β-catenin, and cyclin D1. Further investigation using m⁶A-IP and CLIP assays suggested an association between YTHDF1 and m⁶A-modified SATB1 RNA. To validate the regulatory effect of YTHDF1 on SATB1 in vivo, we established a xenograft mouse model. Knockdown of YTHDF1 significantly suppressed the growth of CNE-2R cells and downregulated SATB1 expression. Overall, our study preliminarily suggests that YTHDF1 knockdown induces tumor cell apoptosis by inhibiting the SATB1/Wnt1/β-catenin pathway, implicating YTHDF1 as a potential regulator of radiosensitivity.