Functional roles and mechanisms of NAT10-mediated RNA ac4C modification in normal development and cancer progression

N-acetyltransferase 10 (NAT10), the primary writer of N4-acetylcytidine (ac 4 C) on RNA, is broadly upregulated across multiple cancer types and correlates with tumor proliferation, invasion, therapeutic resistance, and poor prognosis, indicating its significant clinical relevance. In this mini review, we systematically summarize the functional roles and mechanisms of NAT10-mediated ac 4 C modification in both normal development and cancer. Specifically, we cover recent advances in the regulation of mRNA stability and translation, as well as modifications of tRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). Moreover, we integrate evidence supporting the essential roles of NAT10 in embryonic development, gametogenesis, stem cell self-renewal and differentiation, cellular architecture and cell cycle control, and immune cell expansion, while outlining its oncogenic contributions to tumor growth, metastasis, metabolic reprogramming, drug resistance, and immune evasion. Based on clinical findings, we discuss the potential of NAT10 as a diagnostic and prognostic biomarker and its application in liquid biopsy, and we evaluate the therapeutic potential and limitations of targeting NAT10, including toxicity, specificity, and resistance. Finally, we propose future research directions, including the tumor-specific mechanisms driving NAT10 upregulation, strategies for selectively targeting cancer versus normal physiology, identification of ac 4 C readers and erasers, and potential crosstalk between ac 4 C and chromatin modification, with the aim of advancing NAT10-based precision oncology.