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Literature DB >> 28344040

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

Sicong Zhang¹, Boxuan Simen Zhao², Aidong Zhou³, Kangyu Lin³, Shaoping Zheng³, Zhike Lu², Yaohui Chen³, Erik P Sulman⁴, Keping Xie⁵, Oliver Bögler¹, Sadhan Majumder⁶, Chuan He⁷, Suyun Huang⁸.

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.

Entities: Chemical

Keywords: ALKBH5; FOXM1; glioblastoma; m(6)A modification

Mesh：

Substances：

Year: 2017 PMID： 28344040 PMCID： PMC5427719 DOI： 10.1016/j.ccell.2017.02.013

Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743

50 in total

1. N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency.

Authors: Xiao Wang; Boxuan Simen Zhao; Ian A Roundtree; Zhike Lu; Dali Han; Honghui Ma; Xiaocheng Weng; Kai Chen; Hailing Shi; Chuan He
Journal: Cell Date: 2015-06-04 Impact factor: 41.582

2. Physical isolation of nascent RNA chains transcribed by RNA polymerase II: evidence for cotranscriptional splicing.

Authors: J Wuarin; U Schibler
Journal: Mol Cell Biol Date: 1994-11 Impact factor: 4.272

3. m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells.

Authors: Pedro J Batista; Benoit Molinie; Jinkai Wang; Kun Qu; Jiajing Zhang; Lingjie Li; Donna M Bouley; Ernesto Lujan; Bahareh Haddad; Kaveh Daneshvar; Ava C Carter; Ryan A Flynn; Chan Zhou; Kok-Seong Lim; Peter Dedon; Marius Wernig; Alan C Mullen; Yi Xing; Cosmas C Giallourakis; Howard Y Chang
Journal: Cell Stem Cell Date: 2014-10-16 Impact factor: 24.633

4. Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells.

Authors: David L Schonberg; Tyler E Miller; Qiulian Wu; William A Flavahan; Nupur K Das; James S Hale; Christopher G Hubert; Stephen C Mack; Awad M Jarrar; Robert T Karl; Ann Mari Rosager; Anne M Nixon; Paul J Tesar; Petra Hamerlik; Bjarne W Kristensen; Craig Horbinski; James R Connor; Paul L Fox; Justin D Lathia; Jeremy N Rich
Journal: Cancer Cell Date: 2015-10-12 Impact factor: 31.743

5. Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons.

Authors: Kate D Meyer; Yogesh Saletore; Paul Zumbo; Olivier Elemento; Christopher E Mason; Samie R Jaffrey
Journal: Cell Date: 2012-05-17 Impact factor: 41.582

6. High-resolution N(6) -methyladenosine (m(6) A) map using photo-crosslinking-assisted m(6) A sequencing.

Authors: Kai Chen; Zhike Lu; Xiao Wang; Ye Fu; Guan-Zheng Luo; Nian Liu; Dali Han; Dan Dominissini; Qing Dai; Tao Pan; Chuan He
Journal: Angew Chem Int Ed Engl Date: 2014-12-09 Impact factor: 15.336

7. 5' UTR m(6)A Promotes Cap-Independent Translation.

Authors: Kate D Meyer; Deepak P Patil; Jun Zhou; Alexandra Zinoviev; Maxim A Skabkin; Olivier Elemento; Tatyana V Pestova; Shu-Bing Qian; Samie R Jaffrey
Journal: Cell Date: 2015-10-22 Impact factor: 41.582

8. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells.

Authors: Zhizhong Li; Shideng Bao; Qiulian Wu; Hui Wang; Christine Eyler; Sith Sathornsumetee; Qing Shi; Yiting Cao; Justin Lathia; Roger E McLendon; Anita B Hjelmeland; Jeremy N Rich
Journal: Cancer Cell Date: 2009-06-02 Impact factor: 31.743

9. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.

Authors: Guanqun Zheng; John Arne Dahl; Yamei Niu; Peter Fedorcsak; Chun-Min Huang; Charles J Li; Cathrine B Vågbø; Yue Shi; Wen-Ling Wang; Shu-Hui Song; Zhike Lu; Ralph P G Bosmans; Qing Dai; Ya-Juan Hao; Xin Yang; Wen-Ming Zhao; Wei-Min Tong; Xiu-Jie Wang; Florian Bogdan; Kari Furu; Ye Fu; Guifang Jia; Xu Zhao; Jun Liu; Hans E Krokan; Arne Klungland; Yun-Gui Yang; Chuan He
Journal: Mol Cell Date: 2012-11-21 Impact factor: 17.970

10. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis.

Authors: Xu Zhao; Ying Yang; Bao-Fa Sun; Yue Shi; Xin Yang; Wen Xiao; Ya-Juan Hao; Xiao-Li Ping; Yu-Sheng Chen; Wen-Jia Wang; Kang-Xuan Jin; Xing Wang; Chun-Min Huang; Yu Fu; Xiao-Meng Ge; Shu-Hui Song; Hyun Seok Jeong; Hiroyuki Yanagisawa; Yamei Niu; Gui-Fang Jia; Wei Wu; Wei-Min Tong; Akimitsu Okamoto; Chuan He; Jannie M Rendtlew Danielsen; Xiu-Jie Wang; Yun-Gui Yang
Journal: Cell Res Date: 2014-11-21 Impact factor: 25.617

518 in total

Review 1. The Untranslated Regions of mRNAs in Cancer.

Authors: Samantha L Schuster; Andrew C Hsieh
Journal: Trends Cancer Date: 2019-03-22

2. N⁶-methyladenine DNA Modification in Glioblastoma.

Authors: Qi Xie; Tao P Wu; Ryan C Gimple; Zheng Li; Briana C Prager; Qiulian Wu; Yang Yu; Pengcheng Wang; Yinsheng Wang; David U Gorkin; Cheng Zhang; Alexis V Dowiak; Kaixuan Lin; Chun Zeng; Yinghui Sui; Leo J Y Kim; Tyler E Miller; Li Jiang; Christine H Lee; Zhi Huang; Xiaoguang Fang; Kui Zhai; Stephen C Mack; Maike Sander; Shideng Bao; Amber E Kerstetter-Fogle; Andrew E Sloan; Andrew Z Xiao; Jeremy N Rich
Journal: Cell Date: 2018-11-01 Impact factor: 41.582

3. N⁶-Methylation of Adenosine of FZD10 mRNA Contributes to PARP Inhibitor Resistance.

Authors: Takeshi Fukumoto; Hengrui Zhu; Timothy Nacarelli; Sergey Karakashev; Nail Fatkhutdinov; Shuai Wu; Pingyu Liu; Andrew V Kossenkov; Louise C Showe; Stephanie Jean; Lin Zhang; Rugang Zhang
Journal: Cancer Res Date: 2019-04-09 Impact factor: 12.701

4. FTO-Dependent N ⁶-Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling.

Authors: Hao Huang; Yinu Wang; Manoj Kandpal; Guangyuan Zhao; Horacio Cardenas; Yanrong Ji; Anusha Chaparala; Edward J Tanner; Jianjun Chen; Ramana V Davuluri; Daniela Matei
Journal: Cancer Res Date: 2020-06-30 Impact factor: 12.701

5. m⁶A mRNA methylation regulates testosterone synthesis through modulating autophagy in Leydig cells.

Authors: Yabing Chen; Jing Wang; Dihui Xu; Zou Xiang; Jie Ding; Xiaoyu Yang; Dongmei Li; Xiaodong Han
Journal: Autophagy Date: 2020-01-31 Impact factor: 16.016

6. N^6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.

Authors: Honghui Ma; Xiaoyun Wang; Jiabin Cai; Qing Dai; S Kundhavai Natchiar; Ruitu Lv; Kai Chen; Zhike Lu; Hao Chen; Yujiang Geno Shi; Fei Lan; Jia Fan; Bruno P Klaholz; Tao Pan; Yang Shi; Chuan He
Journal: Nat Chem Biol Date: 2018-12-10 Impact factor: 15.040

10. Adenylate Kinase 4 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an m⁶A-Based Epitranscriptomic Mechanism.

Authors: Xiaochuan Liu; Gwendolyn Gonzalez; Xiaoxia Dai; Weili Miao; Jun Yuan; Ming Huang; David Bade; Lin Li; Yuxiang Sun; Yinsheng Wang
Journal: Mol Ther Date: 2020-09-05 Impact factor: 11.454

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

1. N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency.

2. Physical isolation of nascent RNA chains transcribed by RNA polymerase II: evidence for cotranscriptional splicing.

3. m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells.

4. Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells.

5. Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons.

6. High-resolution N(6) -methyladenosine (m(6) A) map using photo-crosslinking-assisted m(6) A sequencing.

7. 5' UTR m(6)A Promotes Cap-Independent Translation.

8. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells.

9. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.

10. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis.

Review 1. The Untranslated Regions of mRNAs in Cancer.

2. N⁶-methyladenine DNA Modification in Glioblastoma.

3. N⁶-Methylation of Adenosine of FZD10 mRNA Contributes to PARP Inhibitor Resistance.

4. FTO-Dependent N ⁶-Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling.

5. m⁶A mRNA methylation regulates testosterone synthesis through modulating autophagy in Leydig cells.

6. N^6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.

Review 7. Where, When, and How: Context-Dependent Functions of RNA Methylation Writers, Readers, and Erasers.

8. KIAA1429 promotes osteosarcoma progression by promoting stem cell properties and is regulated by miR-143-3p.

Review 9. m⁶A RNA Methylation Controls Neural Development and Is Involved in Human Diseases.

10. Adenylate Kinase 4 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an m⁶A-Based Epitranscriptomic Mechanism.

Review 1. The Untranslated Regions of mRNAs in Cancer.

Review 7. Where, When, and How: Context-Dependent Functions of RNA Methylation Writers, Readers, and Erasers.

Review 9. m6A RNA Methylation Controls Neural Development and Is Involved in Human Diseases.

Review 9. m⁶A RNA Methylation Controls Neural Development and Is Involved in Human Diseases.