Mechanistic study of METTL3 inducing ferroptosis to promote cervical cancer progression through mediating m6A modification of COTE-1.

Cervical Cancer (CC) is one of the leading causes of tumor-related deaths among women worldwide, and the mechanisms underlying the anti-ferroptosis of CC cells are still unclear. Methyltransferase like 3 (METTL3) is widely expressed various types of tissues and plays a crucial role in tumorigenesis in part by mediating cell death. However, its regulatory function in CC progression and especially the underlying mechanisms have not been fully elucidated. This study aims to explore the role of METTL3 in the ferroptosis of CC cells. Mechanistically, by MeRIP-seq, we identified COTE-1 as a target of METTL3 mediated m6A modification, and revealed that METTL3-mediated COTE-1 expression was dependent on the m6A reader-dependent manner. Functionally, in vitro and in vivo experiments that METTL3 promotes proliferation and metastasis of CC cells by regulating COTE-1 expression. In addition, the study verified the effect of the METTL3/COTE-1 axis on autophagy-dependent ferroptosis. In summary, METTL3 influences CC progression by mediating COTE-1 to influence autophagy-dependent ferroptosis, representing a potential therapeutic approach for treating CC.