[1]谭坤铭,黎 盼,衣艳梅.N4-乙酰胞苷修饰在非小细胞肺癌耐药中的作用机制研究进展[J].陕西医学杂志,2026,(5):709-713.[doi:DOI:10.3969/j.issn.1000-7377.2026.05.024]
　TAN Kunming,LI Pan,YI Yanmei.Research progress on the mechanism of N4-acetylcytidine modification in drug resistance of non-small cell lung cancer[J].,2026,(5):709-713.[doi:DOI:10.3969/j.issn.1000-7377.2026.05.024]
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N4-乙酰胞苷修饰在非小细胞肺癌耐药中的作用机制研究进展

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年5期
页码:
709-713
栏目:
综述
出版日期:
2026-05-05

文章信息/Info

Title:
Research progress on the mechanism of N4-acetylcytidine modification in drug resistance of non-small cell lung cancer
作者:
谭坤铭1; 黎 盼2; 衣艳梅1
（1.广东医科大学基础医学院，广东 湛江 524023；2.华中科技大学同济医学院附属协和医院病理科，湖北 武汉 430022）
Author(s):
TAN Kunming1; LI Pan2; YI Yanmei1
(1.School of Basic Medical Sciences,Guangdong Medical University,Zhanjiang 524023,China;2.Department of Pathology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)
关键词:
非小细胞肺癌; N4-乙酰胞苷; N-乙酰基转移酶10; 乙酰化修饰; 耐药性
Keywords:
Non-small cell lung cancer; N4-acetylcytidine; N-acetyltransferase 10; Acetylation modification; Drug resistance
分类号:
R734.2
DOI:
DOI:10.3969/j.issn.1000-7377.2026.05.024
文献标志码:
A
摘要:
肺癌是全球癌症相关死亡的主要原因，其中非小细胞肺癌(NSCLC)占所有肺癌病例的85%以上。化疗、靶向治疗及免疫治疗是NSCLC的主要治疗手段，但耐药性的产生严重制约了临床疗效，成为改善患者预后的关键障碍。N4-乙酰胞苷(ac4C)作为真核生物RNA中唯一已知的乙酰化修饰，由N-乙酰基转移酶10(NAT10)催化形成，通过调控mRNA稳定性、翻译效率及信号通路激活等过程，在肿瘤发生和发展中发挥重要作用。近年来研究表明，ac4C修饰异常与NSCLC的药物敏感性密切相关，其介导的基因表达调控网络可能是耐药形成的重要分子机制。本文系统综述了ac4C修饰的基本生物学特征，重点探讨其在NSCLC化疗、靶向治疗及免疫治疗耐药中的核心作用机制，并总结当前靶向ac4C修饰的治疗策略，为克服NSCLC耐药提供新的理论依据和研究方向。
Abstract:
Lung cancer is the leading cause of cancer-related death worldwide,among which non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancer cases.Chemotherapy,targeted therapy and immunotherapy are the main treatments for NSCLC.However,the development of drug resistance severely restricts the clinical efficacy and has become a key obstacle to improving patient prognosis.As the only known acetylation modification in eukaryotic RNA,N4-acetylcytidine (ac4C) is catalyzed by N-acetyltransferase 10 (NAT10) and plays an important role in tumorigenesis and development by regulating mRNA stability,translation efficiency,signaling pathway activation and other processes.Recent studies have shown that aberrant ac4C modification is closely associated with drug sensitivity in NSCLC,and the gene expression regulatory network mediated by ac4C may be an important molecular mechanism underlying drug resistance.This article systematically reviews the basic biological characteristics of ac4C modification,focuses on its core mechanism in drug resistance of NSCLC during chemotherapy,targeted therapy and immunotherapy,and summarizes current therapeutic strategies targeting ac4C modification,so as to provide new theoretical basis and research directions for overcoming NSCLC drug resistance.

参考文献/References:

[1]SUNG H,FERLAY J,SIEGEL R L,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin，2021，71(3):209-249.
[2]HERBST R S,MORGENSZTERN D,BOSHOFF C.The biology and management of non-small cell lung cancer[J].Nature，2018，553(7689):446-454.
[3]HIRSCH F R,SCAGLIOTTI G V,MULSHINE J L,et al.Lung cancer:Current therapies and new targeted treatments[J].Lancet，2017,389(10066):299-311.
[4]FRYE M,HARADA B T,BEHM M,et al.RNA modifications modulate gene expression in development and cancer[J].Nat Rev Cancer，2018,18(10):647-649.
[5]史庆华.Nat10调控精子发生:生殖生物学研究中的新表观转录组学研究前沿[J].科学通报,2025,70(13):1851-1852.
[6]农巧红,余少康,卢婵妃,等.NAT10介导ac4C乙酰化修饰促进乳腺癌细胞的增殖和迁移能力[J].中国优生与遗传杂志,2024,32(9):1777-1790.
[7]贺胤铭,孔素东,林建国,等.N4-乙酰胞苷RNA检测技术的研究进展[J].高等学校化学学报,2023,44(3):167-174.
[8]唐竞桐.4-乙酰胞苷的形成、功能及其与疾病的关联性研究进展[J].海南医学,2022,33(20):2701-2706.
[9]刘思成.NAT10介导mRNAac4C乙酰化修饰参与消化系统恶性肿瘤发生发展的作用研究[D].成都:四川大学,2023.
[10]WANG Z,HUANG Y,LU W,et al.C-myc-mediated upregulation of NAT10 facilitates tumor development via cell cycle regulation in non-small cell lung cancer[J].Med Oncol,2022,14,39(10):140.
[11]MA X,JIN S,ZHANG X,et al.Targeting the NAT10-HDAC4 positive feedback loop counteracts immunosuppression in breast cancer[J].J Exp Clin Cancer Res,2026,45(1):35.
[12]ARANGO D,STURGILL D,YANG R,et al.Direct epitranscriptomic regulation of mammalian translation initiation through N4-acetylcytidine[J].Mol Cell,2022,82(15):2797-2814.
[13]LARRIEU D,BRITTON S,DEMIR M,et al.Chemical inhibition of NAT10 corrects defects of laminopathic cells[J].Science,2014,344(6183):527-532.
[14]郭向飞,郝颖,赵烨,等.N-乙酰基转移酶10的研究进展[J].生命的化学,2020,40(11):2014-2019.
[15]柘钞,赵峻秀,方嘉雯,等.N4-乙酰胞苷修饰的基本特征及其在肿瘤进展和治疗中的作用[J].中国医学前沿杂志:电子版,2025,17(12):58-68.
[16]刘英竹,程先硕,蔡昕怡,等.结直肠癌中NAT10与上皮-间质转化的关系[J].临床与实验病理学杂志,2022,38(6):742-745.
[17]FENG Z,LI K,QIN K,et al.The LINC00623/NAT10 signaling axis promotes pancreatic cancer progression by remodeling ac4C modification of mRNA[J].J Hematol Oncol,2022,15(1):112.
[18]占关丽.ac4C乙酰转移酶NAT10调控细胞自噬的机制研究[D].武汉:华中科技大学,2024.
[19]周海倩,金浩洁银,张家玮,等.mRNA乙酰化修饰在神经系统的功能研究进展[J].生理科学进展,2024,55(5):385-392.
[20]张雪,汤华.乙酰转移酶10通过介导盘状蛋白结构域受体1 mRNA的ac4C乙酰化修饰促进宫颈癌细胞的恶性行为[J].中国生物化学与分子生物学报,2022,38(5):603-613.
[21]DAI L,TAN Q,LI L,et al.High-throughput antigen microarray identifies longitudinal prognostic autoantibody for chemoimmunotherapy in advanced non-small cell lung cancer[J].Mol cell proteomics,2024,23(5):100749.
[22]王星翔,赵颖,任俏同,等.M2巨噬细胞通过调控NF-κB信号通路对非小细胞肺癌A549细胞上皮-间质转化和顺铂耐药的促进作用[J].吉林大学学报（医学版）,2025,51(3):642-652.
[23]郑传会,林莉,汪霞,等.Wnt/β-catenin信号通路在miR-21介导的非小细胞肺癌顺铂耐药性中的作用[J].西安交通大学学报（医学版）,2025,46(2):238-248.
[24]郝忠慧,赵辰辰,罗洋.非小细胞肺癌顺铂化疗耐药机制及最新进展[J].中国实验诊断学,2025,29(6):736-744,封3.
[25]丁玺.基于生物信息学的紫杉醇类似物对微管蛋白结合行为及稳定性分子机制研究[D].南通:南通大学,2023.
[26]吴平平,李苏宜.紫杉醇耐药与β微管蛋白的研究进展[J].临床肿瘤学杂志,2008,13(8):755-757.
[27]刘萍,王豪勋,王海莉.非小细胞肺癌β-微管蛋白Ⅲ表达及其与含紫杉醇方案耐药的关系[J].实用临床医药杂志,2013,17(3):12-15.
[28]陈矾,焦晓飞,张嘉宇,等.N-乙酰基转移酶10的功能研究进展[J].华南国防医学杂志,2017,31(6):428-430.
[29]WANG S,LI Q,WANG Y,et al.Peptidylprolyl isomerase D circular RNA sensitizes breast cancer to trastuzumab through remodeling HER2 N4-acetylcytidine modification[J].J Appl Genet,2024,65(4):797-807.
[30]ZONG G,WANG X,GUO X,et al.NAT10-mediatedAXL mRNA N4-acetyleytidine modification promotes pan-creatic carcinoma progression[J].Exp Cell Res,2023,428(2):1-11.
[31]郑明.肺腺癌肿瘤免疫微环境及其与疗效和预后的关系[J].中国肿瘤生物治疗杂志,2023,30(8):733-738.
[32]GUPTA R,RADHAKRISHNAN R,KABEKKODU S P,et al.Application of in vitro and in vivo cancer models to study the impact of the tumor immune microenvironment on anticancer therapy[J].Biochim Biophys Acta Rev Cancer,2026,1881(1):189504.
[33]KANG X,CHEN W,ZHANG Y,et al.A sono-responsive nanoplatform integrating STING activation and CXCR4 blockade for synergistic immunotherapy of glioblastoma[J].Adv Mater,2026,38(7):12104.
[34]YANG G,ZHU X,WEI W,et al.Unlocking the role of prostate transmembrane androgen inducible protein 1 in gemcitabine resistance:Modulation of P38-mitogen-activated protein kinase/C-C motif chemokine ligand 2 and M2 macrophage polarization in bladder cancer[J].Anticancer Drugs,2026,37(1):28-39.
[35]SHI Z,SHEN Y,LIU X,et al.Guanylate-binding proteins score and a CBFA2T3-included risk model define immune microenvironment and chemosensitivity in lung adenocarcinoma[J].Eur J Med Res,2025,31(1):124.
[36]PARK N,JEON S H,KIM Y,et al.Akt inhibition enhances the antitumor efficacy of immune checkpoint blockades and radiotherapy in a syngeneic breast cancer model[J].Mol Ther Oncol,2025,33(4):201087.
[37]LIU S,ZHANG Y,QIU L,et al.Uncovering N4-acetylcytidine-related mRNA modification pattern and landscape of stemness and immunity in hepatocellular carcinoma[J].Front Cell Dev Biol,2022,14(10):861000.
[38]申有承.NAT10介导的ac4C在PAH中的功能研究[D].遵义:遵义医科大学,2022.
[39]PAN Y,ZHANG Y,TENG X,et al.Role of NAT10-mediated RNA acetylation in premature ovarian insufficiency:A mechanistic review[J].Gynecol Endocrinol,2026,42(1):2610551.
[40]AO K,SUN Z,HAO Y,et al.Targeted NAT10 degradation by PROTAC NP1192 suppresses hypoxia-adaptive glycolysis and reinvigorates CD8+ effector Tcell function for synergistic cancer immunotherapy[J].ACS Cent Sci,2025,11(11):2087-2107.
[41]LI Y,GAO J,XIAO Y,et al.Deciphering the role of N-acetyltransferase 10 in thalamic hemorrhage through integrative multi-omics and experimental validation[J].J Integr Neurosci,2025,24(11):44643.
[42]WAN X,WANG L,KHAN MA,et al.NAT10-mediated N4-acetylcytidine modification in KLF9 mRNA promotes adipogenesis[J].Cell Death Differ,2025,32(9):1613-1629.
[43]PENG X,LI P,ZHANG Y,et al.Aging increases susceptibility to liver fibrosis through enhanced NAT10-mediated ac4C modification of TGFβ1 mRNA[J].Genome Med,2025,17(1):90.
[44]LEI X,ZHENG B,PENG Y,et al.Targeting the NAT10/XIST/YAP1 axis-mediated vascular abnormalization enhances immune checkpoint blockade in gastric cancer[J].Int J Biol Sci,2025,21(11):4997-5014.
[45]NI Z,CAI L,TSAI I C,et al.NAT10 regulates LPS-induced inflammation via stabilization of N4-acetylated PTX3 mRNA in human dental pulp stem cells[J].Int J Mol Sci,2025,26(9):4325.
[46]王晨红,宋丹,郑勇斌.N-乙酰转移酶10参与结直肠癌铁死亡抵抗[J].中华实验外科杂志,2023,40(3):421-423.
[47]GUO Q,YU W,TAN J,et al.Remodelin delays non-small cell lung cancer progression by inhibiting NAT10 via the EMT pathway[J].Cancer Med,2024,13(11):e7283.
[48]LIU W C,WEI Y H,CHEN J F,et al.Inhibition of tumor-intrinsic NAT10 enhances antitumor immunity by triggering type Ⅰ interferon response via MYC/CDK2/DNMT1 pathway[J].Nat Commun,2025,16(1):5154.
[49]JIN C,WANG T,ZHANG D,et al.Acetyltransferase NAT10 regulates the Wnt/β-catenin signaling pathway to promote colorectal cancer progression via ac4C acetylation of KIF23 mRNA[J].J Exp Clin Cancer Res,2022,41(1):345.
[50]XIE R,CHENG L,HUANG M,et al.NAT10 drivescisplatin chemoresistance by enhancing ac4C-associatedDNA repair in bladder cancer[J].Cancer Res,2023,83(10):1666-1683.
[51]LI G,MA X,SUI S,et al.NAT10/ac4C/JunB facilitates TNBC malignant progression and immunosuppression by driving glycolysis addiction[J].J Exp Clin Cancer Res,2024,43(1):278.
[52]CHEN J,XUE M,MI S,et al.Targeting NAT10 alleviates colonic senescence and elderly-onset colitis by disrupting N4-acetylation of DYRK1A[J].Nat Commun,2026,17(1):3311.
[53]ZHANG Y,DONG Y,CHEN S,et al.Targeting NAT10 inhibits hepatocarcinogenesis via ac4C-mediated SMAD3 mRNA stability[J].Exploration (Beijing),2025,5(6):20250075.
[54]LIU H,ZHANG X,LU Q,et al.NAT10 contributes to the progression of multiple myeloma through ac4C modification of GPR37[J].Hematology,2025,30(1):2555779.
[55]CHEN S,OU W,LI X,et al.NAT10-mediated ac4C modification of KDM1B drives osteoarthritis progression through epigenetic suppression of SOX9[J].Cell Mol Life Sci,2025,82(1):422.
[56]ZHANG X,SHAO R.LncRNA SNHG8 upregulates MUC5B to induce idiopathic pulmonary fibrosis progression by targeting miR-4701-5p[J].Heliyon,2023,10(1):23233.
[57]YUAN S,LIU Q,HU Z,et al.Long non-coding RNA MUC5B-AS1 promotes metastasis through mutually regulating MUC5B expression in lung adenocarcinoma[J].Cell Death Dis,2018,9(5):450.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（82473392）；广东省基础与应用基础研究基金资助项目（2025A1515012650）
更新日期/Last Update: 2026-05-05