The m⁶A Methylation-Regulated AFF4 Promotes Self-Renewal of Bladder Cancer Stem Cells.

ABSTRACT: 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

SUBMITTER: Gao Q 

PROVIDER: S-EPMC7352121 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature