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  • Title: m6A writer WTAP targets NRF2 to accelerate bladder cancer malignancy via m6A-dependent ferroptosis regulation.
    Author: Wang K, Wang G, Li G, Zhang W, Wang Y, Lin X, Han C, Chen H, Shi L, Reheman A, Li J, Li Z, Yang X.
    Journal: Apoptosis; 2023 Apr; 28(3-4):627-638. PubMed ID: 36719469.
    Abstract:
    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 N6-methyladenosine (m6A) in bladder cancer physiological. However, the underlying mechanism of m6A on bladder cancer is still unclear. Here, present work revealed that m6A 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 m6A modification site on 3'-UTR of endogenous antioxidant factor NRF2 RNA and WTAP could install its methylation. Moreover, m6A reader YTHDF1 recognized the m6A site on NRF2 mRNA and enhanced its mRNA stability. Therefore, these findings demonstrated potential therapeutic strategyies for bladder cancer via m6A-dependent manner.
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