NAT10, or N-Acetyltransferase-like protein 10, is the first identified enzyme catalyzing N4-acetylcytidine (ac4C) production in eukaryotic RNA, having acetyltransferase and RNA-binding activities. It plays a significant role in mRNA stability, translation efficiency, oocyte maturation, bone remodeling, and fatty acid metabolism [1].

In multiple diseases, NAT10 has diverse functions. In cancer, knockdown or inhibition of NAT10 in various in-vitro and in-vivo models, including bladder cancer [2,3], cervical cancer [4], multiple myeloma [5], and esophageal cancer [6], reveals its role in promoting tumor cell proliferation, metastasis, and chemoresistance. In sepsis, neutrophil-specific over-expression of NAT10 in mice improves survival and reduces lung injury by inhibiting neutrophil pyroptosis [7]. In periodontitis, the NAT10 inhibitor Remodelin reduces macrophage infiltration and bone resorption in mice [8].

In conclusion, NAT10 is crucial for various biological processes through its ac4C-mediated RNA modification. Studies using gene knockout or conditional knockout models in mice have significantly contributed to understanding its role in cancer, sepsis, and periodontitis, providing potential therapeutic targets for these diseases.

References:

1. Xie, Lihua, Zhong, Xiaolin, Cao, Wenyu, Zu, Xuyu, Chen, Ling. 2023. Mechanisms of NAT10 as ac4C writer in diseases. In Molecular therapy. Nucleic acids, 32, 359-368. doi:10.1016/j.omtn.2023.03.023. https://pubmed.ncbi.nlm.nih.gov/37128278/

2. Xie, Ruihui, Cheng, Liang, Huang, Ming, Chen, Xu, Lin, Tianxin. . NAT10 Drives Cisplatin Chemoresistance by Enhancing ac4C-Associated DNA Repair in Bladder Cancer. In Cancer research, 83, 1666-1683. doi:10.1158/0008-5472.CAN-22-2233. https://pubmed.ncbi.nlm.nih.gov/36939377/

3. Wang, Ganping, Zhang, Ming, Zhang, Yiming, Chen, Binshen, Liu, Chunxiao. . NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression. In Clinical and translational medicine, 12, e738. doi:10.1002/ctm2.738. https://pubmed.ncbi.nlm.nih.gov/35522942/

4. Chen, Xiaona, Hao, Yi, Liu, Yong, Zhang, Jian, Guo, Xia. 2023. NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2302705. doi:10.1002/advs.202302705. https://pubmed.ncbi.nlm.nih.gov/37818745/

5. Wei, Rongfang, Cui, Xing, Min, Jie, Wang, Hongbo, Yang, Ye. 2022. NAT10 promotes cell proliferation by acetylating CEP170 mRNA to enhance translation efficiency in multiple myeloma. In Acta pharmaceutica Sinica. B, 12, 3313-3325. doi:10.1016/j.apsb.2022.01.015. https://pubmed.ncbi.nlm.nih.gov/35967285/

6. Wei, Wei, Zhang, Shuishen, Han, Hui, Choe, Junho, Lin, Shuibin. 2023. NAT10-mediated ac4C tRNA modification promotes EGFR mRNA translation and gefitinib resistance in cancer. In Cell reports, 42, 112810. doi:10.1016/j.celrep.2023.112810. https://pubmed.ncbi.nlm.nih.gov/37463108/

7. Zhang, Hao, Chen, Zhaoyuan, Zhou, Ji'an, Miao, Changhong, Chen, Wankun. 2022. NAT10 regulates neutrophil pyroptosis in sepsis via acetylating ULK1 RNA and activating STING pathway. In Communications biology, 5, 916. doi:10.1038/s42003-022-03868-x. https://pubmed.ncbi.nlm.nih.gov/36068299/

8. Zhang, Zhanqi, Zhang, Yiwen, Cai, Yongjie, Feng, Zhihui, Xu, Qiong. 2023. NAT10 regulates the LPS-induced inflammatory response via the NOX2-ROS-NF-κB pathway in macrophages. In Biochimica et biophysica acta. Molecular cell research, 1870, 119521. doi:10.1016/j.bbamcr.2023.119521. https://pubmed.ncbi.nlm.nih.gov/37307924/