m6A writer WTAP targets NRF2 to accelerate bladder cancer malignancy via m6A-dependent ferroptosis regulation

Recent evidence have indicated that ferroptosis, a novel iron-dependent form of non-apoptotic cell death, plays a critical role in human cancers. Besides, emerging literatures have revealed the ovel function of N 6 -methyladenosine (m 6 A) in bladder cancer physiological. However, the underlying mechanism of m 6 A on bladder cancer is still unclear. Here, present work revealed that m 6 A methyltransferase (‘writer’) WTAP up-regulated in bladder cancer tissue and cells, indicating the poor prognosis of bladder cancer patients. Functionally, gain/loss-of-functional experiments illustrated that WTAP promoted the viability of bladder cancer cells and inhibited the erastin-induced ferroptosis. Mechanistically, there was a remarkable m 6 A modification site on 3’-UTR of endogenous antioxidant factor NRF2 RNA and WTAP could install its methylation. Moreover, m 6 A reader YTHDF1 recognized the m 6 A site on NRF2 mRNA and enhanced its mRNA stability. Therefore, these findings demonstrated potential therapeutic strategyies for bladder cancer via m 6 A-dependent manner.