NAT10: a potential factor to reverse tumor chemotherapy resistance and radioresistance (Review).

NAT10 (N-acetyltransferase 10) is a nucleolar acetyltransferase with catalytic acetylation function, which is currently the only known acetyltransferase that catalyzes the N4-acetylcytidine (ac4C) modification in RNA. As the "writer" protein for ac4C, NAT10 plays a critical role in various biological and pathological processes. In this article, we first introduce the structural and functional characteristics of NAT10, followed by a comprehensive synthesis of its multifaceted molecular mechanisms orchestrating tumor radiotherapy and chemotherapy resistance. Specifically, we emphasize its roles in hyperactivating DNA damage repair (DDR), driving metabolic reprogramming (including evasion of ferroptosis), and facilitating tumor immune evasion via PD-L1 regulation and T-cell suppression. Furthermore, we critically evaluate the translational implications of NAT10-targeted interventions, highlighting the therapeutic promise of specific inhibitors like Remodelin and the repurposed FDA-approved drug Fludarabine. We believe that understanding the functions and mechanisms of NAT10 in tumors will significantly improve the diagnosis, treatment, and prognosis of cancer.