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

被引：1266

作者：

Zhang, Sicong ^{[1
,2
]}

Zhao, Boxuan Simen ^{[3
,4
,5
]}

Zhou, Aidong ^{[1
]}

Lin, Kangyu ^{[1
]}

Zheng, Shaoping ^{[1
]}

Lu, Zhike ^{[3
,4
,5
]}

Chen, Yaohui ^{[1
]}

Sulman, Erik P. ^{[6
]}

Xie, Keping ^{[2
,7
]}

Bogler, Oliver ^{[1
,2
]}

Majumder, Sadhan ^{[8
]}

He, Chuan ^{[3
,4
,5
,9
]}

Huang, Suyun ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Program Canc Biol, UTHlth Grad Sch Biomed Sci, Houston, TX 77030 USA

[3] Univ Chicago, Dept Chem, 5735 S Ellis Ave, Chicago, IL 60637 USA

[4] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA

[5] Univ Chicago, Howard Hughes Med Inst, 5841 S Maryland Ave, Chicago, IL 60637 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA

[9] Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA

来源：

CANCER CELL | 2017年 / 31卷 / 04期

关键词：

MESSENGER-RNA METHYLATION; NUCLEAR-RNA; CROSS-LINKING; PROMOTES; N-6-METHYLADENOSINE; REVEALS; TRANSCRIPTION; TRANSLATION; PROTECTS; TARGET;

D O I：

10.1016/j.ccell.2017.02.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The dynamic and reversible N-6-methyladenosine (m(6)A) RNA modification installed and erased by N-6-methyltransferases and demethylases regulates gene expression and cell fate. We show that the m(6)A demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs. Integrated transcriptome and m(6)A-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 m(6)A methylation in glioblastoma.

引用

页码：591 / +

页数：22

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