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bioRxiv2020

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

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.

cancer biology↗

bioRxiv2019

Temperature dependence of allelopathy duality and its influence on boreal forest succession-A case analysis of Picea schrenkiana

Global warming in conjunction with various biotic or abiotic interferences has been jeopardizing the ecosystem of boreal forests. By integrating field inspection with experimental simulation, this work comprehensively investigated the allelopathic effects of a key allelochemical 3,4-dihydroxyacetophenone (DHAP) in the exudates of P. schrenkiana needles on its seed and seedling growth, endogenous hormone metabolism and antioxidant enzyme activity, identified the existence of DHAP allelopathy duality at a certain temperature with an inflection concentration point (e.g. about 0.25 mM at dark/light temperature of 4/12 {degrees}C) as the boundary between promotional and inhibitory effect, and verified that the inflection point of DHAP concentration would inevitably shift to a lower level as temperature increased. Consequently, this paper gives a scientific explanation into the intrinsic mechanism of P. schrenkiana degradation due to allelopathy, but also presents a new approach to explore the relationship between forest evolution and global warming.\n\nHighlightA quantitative description on the duality of 3, 4-dihydroxyacetophenone (DHAP) as a promoter or an inhibitor to affect the seed germination, seedling growth and root development of P. schrenkiana, as well as the antioxidant enzyme activities and hormone contents.\n\nThe new findings of DHAP inflection concentration as boundary to divide the promotional and inhibitory effect of allelopathy which would decrease as environment temperatures rise.\n\nAn explanation into the intrinsic mechanism of P. schrenkiana degradation due to allelopathy, and a new approach to explore the relationship between forest evolution and global warming.

plant biology↗