METTL14/IGF2BP-mediated m6A methylation of circSLIT2 promotes malignant phenotypes of glioblastoma via the miR-127-5p/SH3GLB1 axis.

Glioblastoma is a highly aggressive and lethal brain tumor that typically originates from glial cells, characterized by rapid growth and resistance to treatment, leading to poor patient prognosis. This study investigates the role and mechanism of the newly discovered circular RNA CircSLIT2 in the malignant progression of glioblastoma. We found that circSLIT2 is significantly overexpressed in glioblastoma cell lines and promotes the proliferation, migration, and invasion of glioblastoma cells by regulating miR-127-5p and upregulating SH3GLB1 expression. In vitro experiments demonstrated that the overexpression of circSLIT2 enhanced cell viability, while treatment with miR-127-5p mimics significantly inhibited this effect. Additionally, we confirmed that CircSLIT2 sponges miR-127-5p, reducing its negative regulation of SH3GLB1 and thereby maintaining SH3GLB1's stable expression. We further revealed the critical roles of METTL14 and IGF2BP1 in the m6A methylation and stability of CircSLIT2. Finally, in a nude mouse model, mice with CircSLIT2 overexpression exhibited significantly larger tumor volumes and shorter survival times, providing further evidence of the important role of CircSLIT2 in glioblastoma development and progression. These findings suggest that CircSLIT2 could serve as a potential molecular target, offering new insights for glioblastoma treatment.