Jiao Lin, Si Yanjun, Yuan Yushan, Lei Xinxing, Jiang Qian, Yang Lijun, Mao Wenhao, Ying Binwu, Ma Liwei, Sun Ting
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
Department of Laboratory Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, China.
Mol Biomed. 2025 Jul 1;6(1):46. doi: 10.1186/s43556-025-00286-3.
N-acetylcytidine (ac4C), a conserved RNA modification, plays critical roles in RNA stability and translation. As the primary enzyme catalyzing ac4C, N-acetyltransferase 10 (NAT10) is increasingly implicated in diverse diseases. This review systematically explores NAT10's multifaceted contributions to cancer, autoimmune disorders, infectious diseases, cardiovascular conditions, and metabolic syndromes. In cancer, NAT10 drives malignancy by enhancing oncogenic processes such as proliferation, metastasis, and therapy resistance, with overexpression linked to poor prognosis across multiple malignancies. Beyond oncology, NAT10 dysregulation is associated with autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus, where it modulates immune responses through RNA acetylation. In infectious contexts, NAT10 influences sepsis progression and viral pathogenesis by stabilizing pathogen-related RNAs, while in cardiovascular diseases, it exacerbates myocardial injury and heart failure through ac4C-dependent and independent pathways. Additionally, NAT10 promotes metabolic dysfunction-associated steatotic liver disease by regulating lipid metabolism genes. The review further discusses therapeutic strategies targeting NAT10, including small-molecule inhibitors and gene silencing approaches, which show promise in preclinical models by suppressing tumor growth, enhancing chemosensitivity, and mitigating inflammatory damage. By integrating molecular insights and clinical relevance, this work underscores NAT10 as a pivotal regulator of disease mechanisms and a potential target for future therapeutic interventions. Future research should address context-dependent roles, refine ac4C detection methods, and explore combinatorial therapies to overcome resistance mechanisms.
N-乙酰胞苷（ac4C）是一种保守的RNA修饰，在RNA稳定性和翻译中发挥关键作用。作为催化ac4C的主要酶，N-乙酰转移酶10（NAT10）越来越多地与多种疾病相关。本综述系统地探讨了NAT10在癌症、自身免疫性疾病、传染病、心血管疾病和代谢综合征等方面的多方面贡献。在癌症中，NAT10通过增强增殖、转移和治疗抗性等致癌过程来驱动恶性肿瘤，其过表达与多种恶性肿瘤的不良预后相关。在肿瘤学之外，NAT10失调与类风湿性关节炎和系统性红斑狼疮等自身免疫性疾病相关，在这些疾病中它通过RNA乙酰化调节免疫反应。在感染情况下，NAT10通过稳定病原体相关RNA影响脓毒症进展和病毒发病机制，而在心血管疾病中，它通过依赖和不依赖ac4C的途径加剧心肌损伤和心力衰竭。此外，NAT10通过调节脂质代谢基因促进代谢功能障碍相关的脂肪性肝病。该综述还讨论了针对NAT10的治疗策略，包括小分子抑制剂和基因沉默方法，这些方法在临床前模型中通过抑制肿瘤生长、增强化学敏感性和减轻炎症损伤显示出前景。通过整合分子见解和临床相关性，这项工作强调了NAT10作为疾病机制的关键调节因子和未来治疗干预的潜在靶点。未来的研究应解决其在不同背景下的作用，完善ac4C检测方法，并探索联合疗法以克服耐药机制。
