NAT10,也称为N-乙酰转移酶10,是一种重要的RNA N4-乙酰胞嘧啶(ac4C)乙酰转移酶。ac4C是一种新兴的RNA修饰,参与调控RNA的稳定性和功能,影响基因表达和生物学过程。NAT10通过催化ac4C修饰,在多种生物学过程中发挥作用,包括细胞增殖、分化、代谢和疾病发生。
NAT10在多种癌症中发挥重要作用,包括膀胱癌、结直肠癌和胃癌。在膀胱癌中,NAT10通过增强DNA损伤修复,促进顺铂化疗耐药性,与患者的不良预后相关[1]。NAT10还通过mRNA ac4C修饰,调节膀胱癌细胞的增殖、迁移、侵袭和干细胞样特性,促进膀胱癌的进展[3]。在结直肠癌中,NAT10通过乙酰化KIF23 mRNA,激活Wnt/β-catenin信号通路,促进结直肠癌的进展[4]。在胃癌中,NAT10通过相分离调节YTHDF1剪接,促进胃癌细胞的增殖和迁移[7]。
NAT10还参与其他生物学过程,如心脏重塑和骨骼肌萎缩。在心脏重塑中,NAT10通过ac4C介导的转录组调控,增强CD47和ROCK2 mRNA的稳定性和翻译效率,导致心脏纤维化、肥厚和炎症反应[2]。在骨骼肌萎缩中,NAT10通过调节ROS/NLRP3信号通路,抑制炎症引起的肌肉萎缩[5]。
此外,NAT10还与脂肪酸代谢相关。NAT10通过乙酰化脂肪酸代谢相关基因的mRNA,如ELOLV6、ACSL1、ACSL3、ACSL4、ACADSB和ACAT1,影响脂肪酸的代谢[6]。
NAT10还与胚胎干细胞的多能性维持相关。NAT10通过催化ac4C修饰,调节核心多能性转录因子OCT4的mRNA稳定性,影响人胚胎干细胞的多能性维持[8]。
综上所述,NAT10是一种重要的RNA乙酰转移酶,通过催化ac4C修饰,在多种生物学过程中发挥作用,包括细胞增殖、分化、代谢和疾病发生。NAT10在多种癌症中发挥重要作用,为癌症的治疗提供了新的靶点。此外,NAT10还参与其他生物学过程,如心脏重塑、骨骼肌萎缩和脂肪酸代谢,为相关疾病的治疗提供了新的思路。
参考文献:
1. 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/
2. Shi, Jing, Yang, Chuanxi, Zhang, Jing, Chen, Lianmin, Kong, Xiangqing. 2023. NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation. In Circulation research, 133, 989-1002. doi:10.1161/CIRCRESAHA.122.322244. https://pubmed.ncbi.nlm.nih.gov/37955115/
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. Jin, Chi, Wang, Tuo, Zhang, Dongsheng, Feng, Yifei, Sun, Yueming. 2022. Acetyltransferase NAT10 regulates the Wnt/β-catenin signaling pathway to promote colorectal cancer progression via ac4C acetylation of KIF23 mRNA. In Journal of experimental & clinical cancer research : CR, 41, 345. doi:10.1186/s13046-022-02551-7. https://pubmed.ncbi.nlm.nih.gov/36522719/
5. Wang, Chuntao, Liu, Yukun, Zhang, Yongsheng, Bai, Xiangjun, Wang, Yuchang. 2023. Targeting NAT10 protects against sepsis-induced skeletal muscle atrophy by inhibiting ROS/NLRP3. In Life sciences, 330, 121948. doi:10.1016/j.lfs.2023.121948. https://pubmed.ncbi.nlm.nih.gov/37467885/
6. Dalhat, Mahmood Hassan, Mohammed, Mohammed Razeeth Shait, Alkhatabi, Hind Ali, Choudhry, Hani, Khan, Mohammad Imran. . NAT10: An RNA cytidine transferase regulates fatty acid metabolism in cancer cells. In Clinical and translational medicine, 12, e1045. doi:10.1002/ctm2.1045. https://pubmed.ncbi.nlm.nih.gov/36149760/
7. Liu, Songyi, Lin, Chunlin, Lin, Xiang, Ye, Jianxin, Zhu, Guangwei. . NAT10 Phase Separation Regulates YTHDF1 Splicing to Promote Gastric Cancer Progression. In Cancer research, 84, 3207-3222. doi:10.1158/0008-5472.CAN-23-4062. https://pubmed.ncbi.nlm.nih.gov/39024555/
8. Liu, Rucong, Wubulikasimu, Zibaguli, Cai, Runze, Zhou, Yuan, Li, Yang. . NAT10-mediated N4-acetylcytidine mRNA modification regulates self-renewal in human embryonic stem cells. In Nucleic acids research, 51, 8514-8531. doi:10.1093/nar/gkad628. https://pubmed.ncbi.nlm.nih.gov/37497776/