D-2-HG Inhibits IDH1mut Glioma Growth via FTO Inhibition and Resultant m6A Hypermethylation

D-2-HG 通过 FTO 抑制和由此产生的 m6A 高甲基化抑制 IDH1mut 胶质瘤生长

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作者:Sean T Pianka #, Tie Li #, Terry J Prins, Blaine S C Eldred, Bryan M Kevan, Haowen Liang, Serendipity Zapanta Rinonos, Harley I Kornblum, David A Nathanson, Matteo Pellegrini, Linda M Liau, Phioanh Leia Nghiemphu, Timothy F Cloughesy, Albert Lai

Significance

We show that IDH1mut-generated D-2-HG can reduce glioma growth via inhibition of the m6A demethylase, FTO. FTO inhibition represents a potential therapeutic target for IDH1wt gliomas and possibly in conjunction with IDH1mut inhibitors for the treatment of IDH1mut glioma. Future studies are necessary to demonstrate the role of ATF5 downregulation in the indolent phenotype of IDH1mut gliomas, as well as to identify other involved gene transcripts deregulated by m6A hypermethylation.

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