The m6A Methylation-Regulated AFF4 Promotes Self-Renewal of Bladder Cancer Stem Cells
Joint Authors
Zhang, Xiuhong
Zheng, Jin
Yuan, Lin
Gao, Qian
Ni, Zegui
Sun, Pengli
Yang, Congcong
Cheng, Maosheng
Wu, Mingqing
Zhang, Yingyin
Li, Yang
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-07-02
Country of Publication
Egypt
No. of Pages
12
Abstract EN
The dynamic N6-methyladenosine (m6A) modification of mRNA plays a role in regulating gene expression and determining cell fate.
However, the functions of m6A mRNA modification in bladder cancer stem cells (BCSCs) have not been described.
Here, we show that global RNA m6A abundance and the expression of m6A-forming enzyme METTL3 are higher in BCSCs than those in non-CSCs of bladder cancer (BCa) cells.
The depletion of the METTL3 inhibited the self-renewal of BCSCs, as evidenced by decreased ALDH activity and sphere-forming ability.
Mechanistically, METTL3 regulates the m6A modification and thereby the expression of AF4/FMR2 family member 4 (AFF4), knockdown of which phenocopies the METTL3 ablation and diminishes the tumor-initiating capability of BCSCs in vivo.
AFF4 binds to the promoter regions and sustains the transcription of SOX2 and MYC which have critical biological functions in BCSCs.
Collectively, our results demonstrate the critical roles of m6A modification in self-renewal and tumorigenicity of BCSCs through a novel signaling axis of METTL3-AFF4-SOX2/MYC.
American Psychological Association (APA)
Gao, Qian& Zheng, Jin& Ni, Zegui& Sun, Pengli& Yang, Congcong& Cheng, Maosheng…[et al.]. 2020. The m6A Methylation-Regulated AFF4 Promotes Self-Renewal of Bladder Cancer Stem Cells. Stem Cells International،Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1207972
Modern Language Association (MLA)
Gao, Qian…[et al.]. The m6A Methylation-Regulated AFF4 Promotes Self-Renewal of Bladder Cancer Stem Cells. Stem Cells International No. 2020 (2020), pp.1-12.
https://search.emarefa.net/detail/BIM-1207972
American Medical Association (AMA)
Gao, Qian& Zheng, Jin& Ni, Zegui& Sun, Pengli& Yang, Congcong& Cheng, Maosheng…[et al.]. The m6A Methylation-Regulated AFF4 Promotes Self-Renewal of Bladder Cancer Stem Cells. Stem Cells International. 2020. Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1207972
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1207972