Matrine suppresses thymoma stemness and apoptosis via YTH N6-methyladenosine RNA binding protein 1 and Wnt/β-catenin signaling.

Thymoma is a mediastinal tumor for which recurrence and therapeutic resistance remain clinical challenges, and cancer stem cell (CSC)-like properties may contribute to these features. This study investigated whether Matrine (Mat) affects stemness-associated features and apoptosis in EL-4-B5 cells and examined the potential involvement of YTHDF1 and Wnt/β-catenin signaling. Mat reduced cell viability and induced apoptosis, with the most evident effects observed at 100 µg/mL. Mat also reduced sphere-forming capacity and CD34 expression. Mat treatment decreased YTHDF1 expression and Wnt3a and β-catenin protein levels, whereas YTHDF1 overexpression or LiCl co-treatment partially attenuated these changes. Public-dataset analyses suggested potential clinical relevance of YTHDF1 in thymoma. Because direct m6A measurements, YTHDF1 target identification, in vivo validation, and clinical-sample validation were not performed, these findings support potential involvement of an m6A-related factor and Wnt/β-catenin signaling rather than establishing a definitive mechanism. Further validation is required before translational conclusions can be made. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-026-04956-z.