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The m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-Like Cells by Sustaining FOXM1 Expression and Cell Proliferation Programing

GSE87515 Homo sapiens Expression profiling by high throughput sequencing; Other 8 samples Submitted 2017/03/28 Platform GPL16791
Summary
The dynamic and reversible N6-methyladenosine (m6A) RNA modification installed and erased by N6-methyltransferases and demethylases regulates gene expression and cell fate. Here, we show that the m6A demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs in vitro and in vivo. Integrated transcriptome and m6A-seq analyses revealed altered expression of select ALKBH5 target genes, including FOXM1, a critical transcription factor for the ALKBH5-dependent cell cycle gene expression. ALKBH5 binds to and demethylates FOXM1 nascent transcripts, leading to enhanced FOXM1 expression. Further, a long noncoding RNA antisense to the FOXM1 (FOXM1-AS) interacts with ALKBH5 and FOXM1 nascent transcripts and promotes their interaction. Depleting ALKBH5 and FOXM1-AS disrupted GSC tumorigenesis through the FOXM1 axis. Our work uncovers a novel function for ALKBH5 in maintaining GSC tumorigenicity and provides insight into critical roles of the m6A RNA methylation in human brain tumor.
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Also filed as BioProject PRJNA345000 and SRA study SRP090686. Searching any of these in the dataset finder brings you back here.

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