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

zhang, m.; yang, c.; liu, x.; ruan, x.; wang, d.; liu, y.; cai, h.; zheng, j.; shao, l.; wang, p.; li, z.; yu, b.; XUE, Y.

doi:10.1101/2020.11.17.387928

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bioRxiv · 10.1101/2020.11.17.387928

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

zhang, m.·yang, c.·liu, x.·ruan, x.·wang, d.·liu, y.·cai, h.·zheng, j.·shao, l.·wang, p.·li, z.·yu, b.·XUE, Y.

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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.

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zhang, m., yang, c., liu, x., ruan, x., wang, d., liu, y., cai, h., zheng, j., shao, l., wang, p., li, z., yu, b., XUE, Y.. 2020-11-18. CPEB2 m6A Methylation Regulates BTB Permeability via Affecting Splicing Factor SRSF5 Stability. https://doi.org/10.1101/2020.11.17.387928

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