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• W3039207958 abstract "The dynamic N 6 -methyladenosine (m 6 A) modification of mRNA plays a role in regulating gene expression and determining cell fate. However, the functions of m 6 A mRNA modification in bladder cancer stem cells (BCSCs) have not been described. Here, we show that global RNA m 6 A abundance and the expression of m 6 A-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 m 6 A 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 m 6 A modification in self-renewal and tumorigenicity of BCSCs through a novel signaling axis of METTL3-AFF4-SOX2/MYC." @default.
• W3039207958 created "2020-07-10" @default.
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• W3039207958 date "2020-07-02" @default.
• W3039207958 modified "2023-10-14" @default.
• W3039207958 title "The m⁶A Methylation-Regulated AFF4 Promotes Self-Renewal of Bladder Cancer Stem Cells" @default.
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• W3039207958 doi "https://doi.org/10.1155/2020/8849218" @default.
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