m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program.

Abstract:

:The dynamic and reversible N6-methyladenosine (m6A) RNA modification installed and erased by N6-methyltransferases and demethylases regulates gene expression and cell fate. 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. Integrated transcriptome and m6A-seq analyses revealed altered expression of certain ALKBH5 target genes, including the transcription factor FOXM1. ALKBH5 demethylates FOXM1 nascent transcripts, leading to enhanced FOXM1 expression. Furthermore, a long non-coding RNA antisense to FOXM1 (FOXM1-AS) promotes the interaction of ALKBH5 with FOXM1 nascent transcripts. Depleting ALKBH5 and FOXM1-AS disrupted GSC tumorigenesis through the FOXM1 axis. Our work uncovers a critical function for ALKBH5 and provides insight into critical roles of m6A methylation in glioblastoma.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Zhang S,Zhao BS,Zhou A,Lin K,Zheng S,Lu Z,Chen Y,Sulman EP,Xie K,Bögler O,Majumder S,He C,Huang S

doi

10.1016/j.ccell.2017.02.013

subject

Has Abstract

pub_date

2017-04-10 00:00:00

pages

591-606.e6

issue

4

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(17)30056-9

journal_volume

31

pub_type

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