CPEB2 m6A Methylation Regulates BTB Permeability via Affecting Splicing Factor SRSF5 Stability

Abstract

The existence of the blood tumor barrier (BTB) severely hinders the delivery of anti-tumor drugs to gliomas, affecting the targeted therapeutic effects of drugs. Therefore, BTB selective opening has become a hot spot for glioma treatment. This study found that the up-regulated METTL3 and IGF2BP3 in GECs increase the stability of CPEB2 mRNA through m6A methylation of CPEB2 mRNA; CPEB2 binds and increases the stability of splicing factor SRSF5 mRNA; SRSF5 promotes the ETS1 exon inclusion; P51-ETS1 promotes the transcriptional expression of tight junction related proteins ZO-1, occludin and claudin-5, regulating BTB permeability. CPEB2, SRSF5 and P51-ETS1 alone or in combination can effectively enhance the role of Dox in promoting glioma cell apoptosis through BTB. The results of this study provide a new theoretical and experimental basis for the molecular regulation of BTB from the perspective of epigenetics, as well as new ideas for the comprehensive treatment of glioma.