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是一种普遍存在于真核细胞RNA上的表观遗传修饰,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,影响mRNA的稳定性和翻译效率,进而调控基因表达和细胞功能。NAT10在多种生物学过程中发挥作用,包括细胞分化、发育、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[1]。NAT10通过mRNA乙酰化修饰,促进膀胱癌细胞增殖、迁移、侵袭和生存,以及干细胞样特性[3]。在结直肠癌中,NAT10通过ac4C修饰KIF23 mRNA,激活Wnt/β-catenin信号通路,促进肿瘤生长和肝肺转移[4]。在胃癌中,NAT10通过相分离调节YTHDF1剪接,促进胃癌细胞增殖和迁移[7]。
NAT10在心脏重塑中也发挥重要作用。NAT10通过ac4C修饰,影响mRNA的稳定性和翻译效率,进而调控基因表达和细胞功能,参与心脏重塑过程[2]。NAT10通过增强CD47和ROCK2 mRNA的稳定性和翻译效率,促进心肌细胞肥大和成纤维细胞活化,进而参与心脏重塑过程[2]。
NAT10还参与炎症反应和肌肉萎缩的调控。NAT10通过NOX2-ROS-NF-κB信号通路,促进巨噬细胞炎症反应[8]。NAT10通过抑制ROS/NLRP3信号通路,抑制炎症引起的肌肉萎缩[5]。NAT10通过乙酰化修饰,促进脂肪酸代谢,影响细胞增殖和上皮间质转化[6]。
NAT10的研究有助于深入理解RNA表观遗传修饰的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。NAT10作为一种重要的RNA乙酰转移酶,在多种生物学过程中发挥重要作用。NAT10的研究有助于深入理解RNA表观遗传修饰的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
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. 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/