Published on April 10, 2017 in Cancer Cell volume 31(4).

PubMed ID: 28344040

DOI: S1535-6108(17)30056-9

Abstract:

The dynamic and reversible N(6)-methyladenosine (m(6)A) RNA modification installedand erased by N(6)-methyltransferases and demethylases regulates gene expression andcell fate. We show that the m(6)A demethylase ALKBH5 is highly expressed inglioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferationof patient-derived GSCs. Integrated transcriptome and m(6)A-seq analyses revealedaltered expression of certain ALKBH5 target genes, including the transcriptionfactor FOXM1. ALKBH5 demethylates FOXM1 nascent transcripts, leading to enhancedFOXM1 expression. Furthermore, a long non-coding RNA antisense to FOXM1 (FOXM1-AS)promotes the interaction of ALKBH5 with FOXM1 nascent transcripts. Depleting ALKBH5and FOXM1-AS disrupted GSC tumorigenesis through the FOXM1 axis. Our work uncovers acritical function for ALKBH5 and provides insight into critical roles of m(6)Amethylation in glioblastoma.CI - Copyright © 2017 Elsevier Inc. All rights reserved.