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image of Emerging Role of NAT10 as ac4C Writer in Inflammatory Diseases: Mechanisms and Therapeutic Applications

Abstract

The incidence of inflammatory diseases, including infections, autoimmune disorders, and tumors, is consistently increasing year by year, posing a significant and growing threat to human health on a global scale. Recent research has indicated that RNA acetylation modification, a specific type of post-transcriptional modification, may play a critical role in the pathogenesis of these diseases. Among the various mechanisms of RNA modification, N-acetyltransferase 10 (NAT10) has been identified as the sole cytidine acetyltransferase in eukaryotes. NAT10 is responsible for acetylating mRNA cytosine, which leads to the formation of N4-acetylcytidine (ac4C), a modification that subsequently influences mRNA stability and translation efficiency. Despite these insights, the specific roles and underlying mechanisms by which RNA acetylation contributes to the onset and progression of inflammatory diseases remain largely unclear. This review aimed to elucidate the alterations in NAT10 expression, the modifications it induces in target genes, and its overall contribution to the pathogenesis of various inflammatory conditions. It has been observed that NAT10 expression tends to increase in most inflammatory conditions, thereby affecting the expression and function of target genes through the formation of ac4C. Furthermore, inhibitors targeting NAT10 present promising therapeutic avenues for treating inflammatory diseases by selectively blocking NAT10 activity, thereby preventing the modification of target genes and suppressing immune cell activation and inflammatory responses. This potential for therapeutic intervention underscores the critical importance of further research on NAT10's role in inflammatory disease pathogenesis, as understanding these mechanisms could lead to significant advancements in treatment strategies, potentially transforming the therapeutic landscape for these conditions.

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2024-11-04
2025-01-29
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References

  1. Medzhitov R. The spectrum of inflammatory responses. Science 2021 374 6571 1070 1075 10.1126/science.abi5200 34822279
    [Google Scholar]
  2. Meizlish M.L. Franklin R.A. Zhou X. Medzhitov R. Tissue Homeostasis and Inflammation. Annu. Rev. Immunol. 2021 39 1 557 581 10.1146/annurev‑immunol‑061020‑053734 33651964
    [Google Scholar]
  3. Netea M.G. Balkwill F. Chonchol M. Cominelli F. Donath M.Y. Giamarellos-Bourboulis E.J. Golenbock D. Gresnigt M.S. Heneka M.T. Hoffman H.M. Hotchkiss R. Joosten L.A.B. Kastner D.L. Korte M. Latz E. Libby P. Mandrup-Poulsen T. Mantovani A. Mills K.H.G. Nowak K.L. O’Neill L.A. Pickkers P. van der Poll T. Ridker P.M. Schalkwijk J. Schwartz D.A. Siegmund B. Steer C.J. Tilg H. van der Meer J.W.M. van de Veerdonk F.L. Dinarello C.A. A guiding map for inflammation. Nat. Immunol. 2017 18 8 826 831 10.1038/ni.3790 28722720
    [Google Scholar]
  4. Sugimoto M.A. Sousa L.P. Pinho V. Perretti M. Teixeira M.M. Resolution of Inflammation: What Controls Its Onset? Front. Immunol. 2016 7 160 10.3389/fimmu.2016.00160 27199985
    [Google Scholar]
  5. Furman D. Campisi J. Verdin E. Carrera-Bastos P. Targ S. Franceschi C. Ferrucci L. Gilroy D.W. Fasano A. Miller G.W. Miller A.H. Mantovani A. Weyand C.M. Barzilai N. Goronzy J.J. Rando T.A. Effros R.B. Lucia A. Kleinstreuer N. Slavich G.M. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 2019 25 12 1822 1832 10.1038/s41591‑019‑0675‑0 31806905
    [Google Scholar]
  6. Falstie-jensen N. Christensen K.S. Brøchner-Mortensen J. Selection of lower limb amputation level not aided by transcutaneous pO 2 measurements. Acta Orthop. Scand. 1989 60 4 483 485 10.3109/17453678909149326 2816330
    [Google Scholar]
  7. Takeuchi O. Akira S. Pattern recognition receptors and inflammation. Cell 2010 140 6 805 820 10.1016/j.cell.2010.01.022 20303872
    [Google Scholar]
  8. Netea M.G. Balkwill F. Chonchol M. Cominelli F. Donath M.Y. Giamarellos-Bourboulis E.J. Golenbock D. Gresnigt M.S. Heneka M.T. Hoffman H.M. Hotchkiss R. Joosten L.A.B. Kastner D.L. Korte M. Latz E. Libby P. Mandrup-Poulsen T. Mantovani A. Mills K.H.G. Nowak K.L. O’Neill L.A. Pickkers P. van der Poll T. Ridker P.M. Schalkwijk J. Schwartz D.A. Siegmund B. Steer C.J. Tilg H. van der Meer J.W.M. van de Veerdonk F.L. Dinarello C.A. Author Correction: A guiding map for inflammation. Nat. Immunol. 2021 22 2 254 10.1038/s41590‑020‑00846‑5 33288963
    [Google Scholar]
  9. Medzhitov R. Origin and physiological roles of inflammation. Nature 2008 454 7203 428 435 10.1038/nature07201 18650913
    [Google Scholar]
  10. Dong C. Niu L. Song W. Xiong X. Zhang X. Zhang Z. Yang Y. Yi F. Zhan J. Zhang H. Yang Z. Zhang L.H. Zhai S. Li H. Ye M. Du Q. tRNA modification profiles of the fast-proliferating cancer cells. Biochem. Biophys. Res. Commun. 2016 476 4 340 345 10.1016/j.bbrc.2016.05.124 27246735
    [Google Scholar]
  11. Sharma S. Langhendries J.L. Watzinger P. Kötter P. Entian K.D. Lafontaine D.L.J. Yeast Kre33 and human NAT10 are conserved 18S rRNA cytosine acetyltransferases that modify tRNAs assisted by the adaptor Tan1/THUMPD1. Nucleic Acids Res. 2015 43 4 2242 2258 10.1093/nar/gkv075 25653167
    [Google Scholar]
  12. Arango D. Sturgill D. Alhusaini N. Dillman A.A. Sweet T.J. Hanson G. Hosogane M. Sinclair W.R. Nanan K.K. Mandler M.D. Fox S.D. Zengeya T.T. Andresson T. Meier J.L. Coller J. Oberdoerffer S. Acetylation of Cytidine in mRNA Promotes Translation Efficiency. Cell 2018 175 7 1872 1886.e24 10.1016/j.cell.2018.10.030 30449621
    [Google Scholar]
  13. Jin G. Xu M. Zou M. Duan S. The Processing, Gene Regulation, Biological Functions, and Clinical Relevance of N4-Acetylcytidine on RNA: A Systematic Review. Mol. Ther. Nucleic Acids 2020 20 13 24 10.1016/j.omtn.2020.01.037 32171170
    [Google Scholar]
  14. Ito S. Horikawa S. Suzuki T. Kawauchi H. Tanaka Y. Suzuki T. Suzuki T. Human NAT10 is an ATP-dependent RNA acetyltransferase responsible for N4-acetylcytidine formation in 18 S ribosomal RNA (rRNA). J. Biol. Chem. 2014 289 52 35724 35730 10.1074/jbc.C114.602698 25411247
    [Google Scholar]
  15. Silva A.P.G. Byrne R.T. Chechik M. Smits C. Waterman D.G. Antson A.A. Expression, purification, crystallization and preliminary X-ray studies of the TAN1 orthologue from Methanothermobacter thermautotrophicus. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2008 64 11 1083 1086 10.1107/S1744309108034039 18997348
    [Google Scholar]
  16. Xu H. Jiang B. Meng L. Ren T. Zeng Y. Wu J. Qu L. Shou C. N -α-Acetyltransferase 10 protein inhibits apoptosis through RelA/p65-regulated MCL1 expression. Carcinogenesis 2012 33 6 1193 1202 10.1093/carcin/bgs144 22496479
    [Google Scholar]
  17. Zhang X. Liu J. Yan S. Huang K. Bai Y. Zheng S. High expression of N-acetyltransferase 10: a novel independent prognostic marker of worse outcome in patients with hepatocellular carcinoma. Int. J. Clin. Exp. Pathol. 2015 8 11 14765 14771 26823802
    [Google Scholar]
  18. Tsai K. Jaguva Vasudevan A.A. Martinez Campos C. Emery A. Swanstrom R. Cullen B.R. Acetylation of Cytidine Residues Boosts HIV-1 Gene Expression by Increasing Viral RNA Stability. Cell Host Microbe 2020 28 2 306 312.e6 10.1016/j.chom.2020.05.011 32533923
    [Google Scholar]
  19. Yan Q. Zhou J. Wang Z. Ding X. Ma X. Li W. Jia X. Gao S.J. Lu C. NAT10-dependent N4-acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation. Nat. Commun. 2023 14 1 6327 10.1038/s41467‑023‑42135‑3 37816771
    [Google Scholar]
  20. Guo G. Shi X. Wang H. Ye L. Tong X. Yan K. Ding N. Chen C. Zhang H. Xue X. Epitranscriptomic N4-Acetylcytidine Profiling in CD4+ T Cells of Systemic Lupus Erythematosus. Front. Cell Dev. Biol. 2020 8 842 10.3389/fcell.2020.00842 32984334
    [Google Scholar]
  21. Shi J. Yang C. Zhang J. Zhao K. Li P. Kong C. Wu X. Sun H. Zheng R. Sun W. Chen L. Kong X. NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation. Circ. Res. 2023 133 12 989 1002 10.1161/CIRCRESAHA.122.322244 37955115
    [Google Scholar]
  22. Yang C. Wu T. Zhang J. Liu J. Zhao K. Sun W. Zhou X. Kong X. Shi J. Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research? Front. Oncol. 2021 11 630417 10.3389/fonc.2021.630417 34094911
    [Google Scholar]
  23. Liu D. Kuang Y. Chen S. Li R. Su F. Zhang S. Qiu Q. Lin S. Shen C. Liu Y. Liang L. Wang J. Xu H. Xiao Y. NAT10 promotes synovial aggression by increasing the stability and translation of N4-acetylated PTX3 mRNA in rheumatoid arthritis. Ann. Rheum. Dis. 2024 83 9 ard-2023-225343 10.1136/ard‑2023‑225343 38724075
    [Google Scholar]
  24. Liu Y. Wang X. Liu Y. Yang J. Mao W. Feng C. Wu X. Chen X. Chen L. Dong P. N4-acetylcytidine-dependent GLMP mRNA stabilization by NAT10 promotes head and neck squamous cell carcinoma metastasis and remodels tumor microenvironment through MAPK/ERK signaling pathway. Cell Death Dis. 2023 14 11 712 10.1038/s41419‑023‑06245‑6 37914704
    [Google Scholar]
  25. Zhang Z. Zhang Y. Cai Y. Li D. He J. Feng Z. Xu Q. NAT10 regulates the LPS-induced inflammatory response via the NOX2-ROS-NF-κB pathway in macrophages. Biochim. Biophys. Acta Mol. Cell Res. 2023 1870 7 119521 10.1016/j.bbamcr.2023.119521 37307924
    [Google Scholar]
  26. Zhang X. Jiang Y. Mao J. Ren X. Ji Y. Mao Y. Chen Y. Sun X. Pan Y. Ma J. Huang S. Hydroxytyrosol prevents periodontitis-induced bone loss by regulating mitochondrial function and mitogen-activated protein kinase signaling of bone cells. Free Radic. Biol. Med. 2021 176 298 311 10.1016/j.freeradbiomed.2021.09.027 34610362
    [Google Scholar]
  27. Wang Z. Luo J. Huang H. Wang L. Lv T. Wang Z. Li C. Wang Y. Liu J. Cheng Q. Zuo X. Hu L. Ye M. Liu H. Song Y. NAT10-mediated upregulation of GAS5 facilitates immune cell infiltration in non-small cell lung cancer via the MYBBP1A-p53/IRF1/type I interferon signaling axis. Cell Death Discov. 2024 10 1 240 10.1038/s41420‑024‑01997‑2 38762546
    [Google Scholar]
  28. Jin C. Gao J. Zhu J. Ao Y. Shi B. Li X. Exosomal NAT10 from esophageal squamous cell carcinoma cells modulates macrophage lipid metabolism and polarization through ac4C modification of FASN. Transl. Oncol. 2024 45 101934 10.1016/j.tranon.2024.101934 38692194
    [Google Scholar]
  29. Duan J. Zhang Q. Hu X. Lu D. Yu W. Bai H. N4-acetylcytidine is required for sustained NLRP3 inflammasome activation via HMGB1 pathway in microglia. Cell. Signal. 2019 58 44 52 10.1016/j.cellsig.2019.03.007 30853521
    [Google Scholar]
  30. Furman D. Chang J. Lartigue L. Bolen C.R. Haddad F. Gaudilliere B. Ganio E.A. Fragiadakis G.K. Spitzer M.H. Douchet I. Daburon S. Moreau J.F. Nolan G.P. Blanco P. Déchanet-Merville J. Dekker C.L. Jojic V. Kuo C.J. Davis M.M. Faustin B. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat. Med. 2017 23 2 174 184 10.1038/nm.4267 28092664
    [Google Scholar]
  31. Demkow U. Neutrophil Extracellular Traps (NETs) in Cancer Invasion, Evasion and Metastasis. Cancers (Basel) 2021 13 17 4495 10.3390/cancers13174495 34503307
    [Google Scholar]
  32. Liu D. Yang X. Wang X. Neutrophil extracellular traps promote gastric cancer cell metastasis via the NAT10-mediated N4-acetylcytidine modification of SMYD2. Cell. Signal. 2024 116 111014 10.1016/j.cellsig.2023.111014 38110168
    [Google Scholar]
  33. Wan W. Liu W. STING recruits WIPI2 for autophagosome formation. Autophagy 2024 20 4 928 929 10.1080/15548627.2023.2202108 37041719
    [Google Scholar]
  34. Zhang H. Chen Z. Zhou J. Gu J. Wu H. Jiang Y. Gao S. Liao Y. Shen R. Miao C. Chen W. NAT10 regulates neutrophil pyroptosis in sepsis via acetylating ULK1 RNA and activating STING pathway. Commun. Biol. 2022 5 1 916 10.1038/s42003‑022‑03868‑x 36068299
    [Google Scholar]
  35. Li Q. Yuan Z. Wang Y. Zhai P. Wang J. Zhang C. Shao Z. Xing C. Unveiling YWHAH: A potential therapeutic target for overcoming CD8+ T cell exhaustion in colorectal cancer. Int. Immunopharmacol. 2024 135 112317 10.1016/j.intimp.2024.112317 38796965
    [Google Scholar]
  36. Townsend A.K. Sewall K.B. Leonard A.S. Hawley D.M. Infectious disease and cognition in wild populations. Trends Ecol. Evol. 2022 37 10 899 910 10.1016/j.tree.2022.06.005 35872026
    [Google Scholar]
  37. Liao Z. He L. Fu J. Zhou X. Li Y. He J. Liu Y. Guo J. Liu S. Identification of novel biomarkers for lupus nephritis. Biomol. Biomed. 2024 10.17305/bb.2024.10450 38980684
    [Google Scholar]
  38. Shacter E. Weitzman S.A. Chronic inflammation and cancer. Oncology (Williston Park) 2002 16 2 217 226 11866137
    [Google Scholar]
  39. Chen D. Zhang X. Li Z. Zhu B. Metabolic regulatory crosstalk between tumor microenvironment and tumor-associated macrophages. Theranostics 2021 11 3 1016 1030 10.7150/thno.51777 33391518
    [Google Scholar]
  40. Li H. Qin Q. Shi X. He J. Xu G. Modified metabolites mapping by liquid chromatography-high resolution mass spectrometry using full scan/all ion fragmentation/neutral loss acquisition. J. Chromatogr. A 2019 1583 80 87 10.1016/j.chroma.2018.11.014 30471789
    [Google Scholar]
  41. Liu X. Tan Y. Zhang C. Zhang Y. Zhang L. Ren P. Deng H. Luo J. Ke Y. Du X. NAT 10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2. EMBO Rep. 2016 17 3 349 366 10.15252/embr.201540505 26882543
    [Google Scholar]
  42. Li Q. Liu X. Jin K. Lu M. Zhang C. Du X. Xing B. NAT10 is upregulated in hepatocellular carcinoma and enhances mutant p53 activity. BMC Cancer 2017 17 1 605 10.1186/s12885‑017‑3570‑4 28859621
    [Google Scholar]
  43. Deng M. Zhang L. Zheng W. Chen J. Du N. Li M. Chen W. Huang Y. Zeng N. Song Y. Chen Y. Helicobacter pylori-induced NAT10 stabilizes MDM2 mRNA via RNA acetylation to facilitate gastric cancer progression. J. Exp. Clin. Cancer Res. 2023 42 1 9 10.1186/s13046‑022‑02586‑w 36609449
    [Google Scholar]
  44. Wang G. Zhang M. Zhang Y. Xie Y. Zou J. Zhong J. Zheng Z. Zhou X. Zheng Y. Chen B. Liu C. NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression. Clin. Transl. Med. 2022 12 5 e738 10.1002/ctm2.738 35522942
    [Google Scholar]
  45. Wei Z. Yang M. Feng M. Wu Z. Rosin-Arbesfeld R. Dong J. Zhu D. Inhibition of BCL9 Modulates the Cellular Landscape of Tumor-Associated Macrophages in the Tumor Immune Microenvironment of Colorectal Cancer. Front. Pharmacol. 2021 12 713331 10.3389/fphar.2021.713331 34566638
    [Google Scholar]
  46. Zong G. Wang X. Guo X. Zhao Q. Wang C. Shen S. Xiao W. Yang Q. Jiang W. Shen J. Wan R. NAT10-mediated AXL mRNA N4-acetylcytidine modification promotes pancreatic carcinoma progression. Exp. Cell Res. 2023 428 2 113620 10.1016/j.yexcr.2023.113620 37156457
    [Google Scholar]
  47. Fukami K. Yamagishi S. Okuda S. Role of AGEs-RAGE system in cardiovascular disease. Curr. Pharm. Des. 2014 20 14 2395 2402 10.2174/13816128113199990475 23844818
    [Google Scholar]
  48. Schmid M.C. Avraamides C.J. Dippold H.C. Franco I. Foubert P. Ellies L.G. Acevedo L.M. Manglicmot J.R.E. Song X. Wrasidlo W. Blair S.L. Ginsberg M.H. Cheresh D.A. Hirsch E. Field S.J. Varner J.A. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kγ, a single convergent point promoting tumor inflammation and progression. Cancer Cell 2011 19 6 715 727 10.1016/j.ccr.2011.04.016 21665146
    [Google Scholar]
  49. Ding M. Yu Z. Lu T. Hu S. Zhou X. Wang X. N -acetyltransferase 10 facilitates tumorigenesis of diffuse large B-cell lymphoma by regulating AMPK/mTOR signalling through N4-acetylcytidine modification of SLC30A9. Clin. Transl. Med. 2024 14 7 e1747 10.1002/ctm2.1747 38961519
    [Google Scholar]
  50. Xu X. Gao W. Li L. Hao J. Yang B. Wang T. Li L. Bai X. Li F. Ren H. Zhang M. Zhang L. Wang J. Wang D. Zhang J. Jiao L. Annexin A1 protects against cerebral ischemia–reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway. J. Neuroinflammation 2021 18 1 119 10.1186/s12974‑021‑02174‑3 34022892
    [Google Scholar]
  51. Chun Y. Kim J. AMPK–mTOR Signaling and Cellular Adaptations in Hypoxia. Int. J. Mol. Sci. 2021 22 18 9765 10.3390/ijms22189765 34575924
    [Google Scholar]
  52. Liao L. He Y. Li S.J. Yu X.M. Liu Z.C. Liang Y.Y. Yang H. Yang J. Zhang G.G. Deng C.M. Wei X. Zhu Y.D. Xu T.Y. Zheng C.C. Cheng C. Li A. Li Z.G. Liu J.B. Li B. Lysine 2-hydroxyisobutyrylation of NAT10 promotes cancer metastasis in an ac4C-dependent manner. Cell Res. 2023 33 5 355 371 10.1038/s41422‑023‑00793‑4 36882514
    [Google Scholar]
  53. Jin C. Wang T. Zhang D. Yang P. Zhang C. Peng W. Jin K. Wang L. Zhou J. Peng C. Tan Y. Ji J. Chen Z. Sun Q. Yang S. Tang J. Feng Y. Sun Y. Acetyltransferase NAT10 regulates the Wnt/β-catenin signaling pathway to promote colorectal cancer progression via ac4C acetylation of KIF23 mRNA. J. Exp. Clin. Cancer Res. 2022 41 1 345 10.1186/s13046‑022‑02551‑7 36522719
    [Google Scholar]
  54. Accapezzato D. Caccavale R. Paroli M.P. Gioia C. Nguyen B.L. Spadea L. Paroli M. Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus. Int. J. Mol. Sci. 2023 24 7 6578 10.3390/ijms24076578 37047548
    [Google Scholar]
  55. Budd R.C. Scharer C.D. Barrantes-Reynolds R. Legunn S. Fortner K.A. T Cell Homeostatic Proliferation Promotes a Redox State That Drives Metabolic and Epigenetic Upregulation of Inflammatory Pathways in Lupus. Antioxid. Redox Signal. 2022 36 7-9 410 422 10.1089/ars.2021.0078 34328790
    [Google Scholar]
  56. Yim L.Y. Lau C.S. Chan V.S.F. Heightened TLR7/9-Induced IL-10 and CXCL13 Production with Dysregulated NF-ҝB Activation in CD11chiCD11b+ Dendritic Cells in NZB/W F1 Mice. Int. J. Mol. Sci. 2019 20 18 4639 10.3390/ijms20184639 31546763
    [Google Scholar]
  57. Smith M.H. Berman J.R. What Is Rheumatoid Arthritis? JAMA 2022 327 12 1194 10.1001/jama.2022.0786 35315883
    [Google Scholar]
  58. Payet M. Dargai F. Gasque P. Guillot X. Epigenetic Regulation (Including Micro-RNAs, DNA Methylation and Histone Modifications) of Rheumatoid Arthritis: A Systematic Review. Int. J. Mol. Sci. 2021 22 22 12170 10.3390/ijms222212170 34830057
    [Google Scholar]
  59. Boulet J. Sridhar V. S. Bouabdallaoui N. Tardif J. C. White M. Inflammation in heart failure: Pathophysiology and therapeutic strategies. Inflamm Res. 2024 73 5 709 723 10.1007/s00011‑023‑01845‑6
    [Google Scholar]
  60. Kumari R. Ranjan P. Suleiman Z.G. Goswami S.K. Li J. Prasad R. Verma S.K. mRNA modifications in cardiovascular biology and disease: with a focus on m6A modification. Cardiovasc. Res. 2022 118 7 1680 1692 10.1093/cvr/cvab160 33956076
    [Google Scholar]
  61. Ge Y. Chen R. Ling T. Liu B. Huang J. Cheng Y. Lin Y. Chen H. Xie X. Xia G. Luo G. Yuan S. Xu A. Elevated WTAP promotes hyperinflammation by increasing m6A modification in inflammatory disease models. J. Clin. Invest. 2024 134 14 e177932 10.1172/JCI177932 39007267
    [Google Scholar]
  62. Qiu L. Jing Q. Li Y. Han J. RNA modification: mechanisms and therapeutic targets. Mol. Biomed. 2023 4 1 25 10.1186/s43556‑023‑00139‑x 37612540
    [Google Scholar]
  63. Wang C. Song S. Zhang Y. Ge Y. Fang X. Huang T. Du J. Gao J. Inhibition of the Rho/Rho kinase pathway prevents lipopolysaccharide-induced hyperalgesia and the release of TNF-α and IL-1β in the mouse spinal cord. Sci. Rep. 2015 5 1 14553 10.1038/srep14553 26416580
    [Google Scholar]
  64. Zanin-Zhorov A. Flynn R. Waksal S.D. Blazar B.R. Isoform-specific targeting of ROCK proteins in immune cells. Small GTPases 2016 7 3 173 177 10.1080/21541248.2016.1181698 27254302
    [Google Scholar]
  65. Biswas P.S. Gupta S. Chang E. Song L. Stirzaker R.A. Liao J.K. Bhagat G. Pernis A.B. Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice. J. Clin. Invest. 2010 120 9 3280 3295 10.1172/JCI42856 20697158
    [Google Scholar]
  66. Kanno S. Hirano S. Chiba S. Takeshita H. Nagai T. Takada M. Sakamoto K. Mukai T. The role of Rho-kinases in IL-1β release through phagocytosis of fibrous particles in human monocytes. Arch. Toxicol. 2015 89 1 73 85 10.1007/s00204‑014‑1238‑2 24760326
    [Google Scholar]
  67. Ministrini S. Carbone F. Montecucco F. Updating concepts on atherosclerotic inflammation: From pathophysiology to treatment. Eur. J. Clin. Invest. 2021 51 5 e13467 10.1111/eci.13467 33259635
    [Google Scholar]
  68. Oliveira J.B. Soares A.A.S.M. Sposito A.C. Inflammatory Response During Myocardial Infarction. Adv. Clin. Chem. 2018 84 39 79 10.1016/bs.acc.2017.12.002 29478516
    [Google Scholar]
  69. Chen Y. Zeng L. Peripheral Inflammatory Factors and Acute Myocardial Infarction Risk: A Mendelian Randomization Study. Glob. Heart 2023 18 1 55 10.5334/gh.1269 37811136
    [Google Scholar]
  70. Broch K. Anstensrud A.K. Woxholt S. Sharma K. Tøllefsen I.M. Bendz B. Aakhus S. Ueland T. Amundsen B.H. Damås J.K. Berg E.S. Bjørkelund E. Bendz C. Hopp E. Kleveland O. Stensæth K.H. Opdahl A. Kløw N.E. Seljeflot I. Andersen G.Ø. Wiseth R. Aukrust P. Gullestad L. Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction. J. Am. Coll. Cardiol. 2021 77 15 1845 1855 10.1016/j.jacc.2021.02.049 33858620
    [Google Scholar]
  71. Rana I. Stebbing M. Kompa A. Kelly D.J. Krum H. Badoer E. Microglia activation in the hypothalamic PVN following myocardial infarction. Brain Res. 2010 1326 96 104 10.1016/j.brainres.2010.02.028 20156424
    [Google Scholar]
  72. Wang K. Zhou L. Y. Liu F. Lin L. Ju J. Tian P. C. Liu C. Y. Li X. M. Chen X. Z. Wang T. Wang F. Wang S. C. Zhang J. Zhang Y. H. Tian J. W. Wang K. PIWI-Interacting RNA HAAPIR Regulates Cardiomyocyte Death After Myocardial Infarction by Promoting NAT10-Mediated ac(4) C Acetylation of Tfec mRNA. Adv. Sci. 2022 9 8 e2106058
    [Google Scholar]
  73. Nutma E. Fancy N. Weinert M. Tsartsalis S. Marzin M.C. Muirhead R.C.J. Falk I. Breur M. de Bruin J. Hollaus D. Pieterman R. Anink J. Story D. Chandran S. Tang J. Trolese M.C. Saito T. Saido T.C. Wiltshire K.H. Beltran-Lobo P. Phillips A. Antel J. Healy L. Dorion M.F. Galloway D.A. Benoit R.Y. Amossé Q. Ceyzériat K. Badina A.M. Kövari E. Bendotti C. Aronica E. Radulescu C.I. Wong J.H. Barron A.M. Smith A.M. Barnes S.J. Hampton D.W. van der Valk P. Jacobson S. Howell O.W. Baker D. Kipp M. Kaddatz H. Tournier B.B. Millet P. Matthews P.M. Moore C.S. Amor S. Owen D.R. Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases. Nat. Commun. 2023 14 1 5247 10.1038/s41467‑023‑40937‑z 37640701
    [Google Scholar]
  74. Qu Z. Pang X. Mei Z. Li Y. Zhang Y. Huang C. Liu K. Yu S. Wang C. Sun Z. Liu Y. Li X. Jia Y. Dong Y. Lu M. Ju T. Wu F. Huang M. Li N. Dou S. Jiang J. Dong X. Zhang Y. Li W. Yang B. Du W. The positive feedback loop of the NAT10/Mybbp1a/p53 axis promotes cardiomyocyte ferroptosis to exacerbate cardiac I/R injury. Redox Biol. 2024 72 103145 10.1016/j.redox.2024.103145 38583415
    [Google Scholar]
  75. Twarowski B. Herbet M. Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review. Int. J. Mol. Sci. 2023 24 7 6518 10.3390/ijms24076518 37047492
    [Google Scholar]
  76. Ma Y. Fan C. Wang Y. Li W. Jiang H. Yang W. Comprehensive analysis of mRNAs in the cerebral cortex in APP/PS1 double- transgenic mice with Alzheimer’s disease based on high-throughput sequencing of N4-acetylcytidine. Funct. Integr. Genomics 2023 23 3 267 10.1007/s10142‑023‑01192‑z 37548859
    [Google Scholar]
  77. Burke J.E. Triscott J. Emerling B.M. Hammond G.R.V. Beyond PI3Ks: targeting phosphoinositide kinases in disease. Nat. Rev. Drug Discov. 2023 22 5 357 386 10.1038/s41573‑022‑00582‑5 36376561
    [Google Scholar]
  78. Cao Y. Chen J. Ren G. Zhang Y. Tan X. Yang L. Punicalagin Prevents Inflammation in LPS- Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway. Nutrients 2019 11 11 2794 10.3390/nu11112794 31731808
    [Google Scholar]
  79. Jiao B. Zhang W. Zhang C. Zhang K. Cao X. Yu S. Zhang X. Protein tyrosine phosphatase 1B contributes to neuropathic pain by aggravating NF-κB and glial cells activation-mediated neuroinflammation via promoting endoplasmic reticulum stress. CNS Neurosci. Ther. 2024 30 2 e14609 10.1111/cns.14609 38334011
    [Google Scholar]
  80. Gao Y. Mei C. Chen P. Chen X. The contribution of neuro-immune crosstalk to pain in the peripheral nervous system and the spinal cord. Int. Immunopharmacol. 2022 107 108700 10.1016/j.intimp.2022.108700 35313271
    [Google Scholar]
  81. Zhang M. Yang K. Wang Q.H. Xie L. Liu Q. Wei R. Tao Y. Zheng H.L. Lin N. Xu H. Yang L. Wang H. Zhang T. Xue Z. Cao J.L. Pan Z. The Cytidine N-Acetyltransferase NAT10 Participates in Peripheral Nerve Injury-Induced Neuropathic Pain by Stabilizing SYT9 Expression in Primary Sensory Neurons. J. Neurosci. 2023 43 17 3009 3027 10.1523/JNEUROSCI.2321‑22.2023 36898834
    [Google Scholar]
  82. Cho M.J. Lee D.G. Lee J.W. Hwang B. Yoon S.J. Lee S.J. Park Y.J. Park S.H. Lee H.G. Kim Y.H. Lee C.H. Lee J. Lee N.K. Han T.S. Cho H.S. Moon J.H. Lee G.S. Bae K.H. Hwang G.S. Lee S.H. Chung S.J. Shim S. Cho J. Oh G.T. Kwon Y.G. Park J.G. Min J.K. Endothelial PTP4A1 mitigates vascular inflammation via USF1/A20 axis-mediated NF-κB inactivation. Cardiovasc. Res. 2023 119 5 1265 1278 10.1093/cvr/cvac193 36534975
    [Google Scholar]
  83. Xu T. Wang J. Wu Y. Wu J. Y. Lu W. C. Liu M. Zhang S. B. Xie D. Xin W. J. Xie J. D. Ac4C Enhances the Translation Efficiency of Vegfa mRNA and Mediates Central Sensitization in Spinal Dorsal Horn in Neuropathic Pain. Adv. Sci. 2023 10 35 e2303113
    [Google Scholar]
  84. Zhu Z. Xing X. Huang S. Tu Y. NAT10 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Mediating N4-Acetylcytidine Modification of Gremlin 1. Stem Cells Int. 2021 2021 1 10 10.1155/2021/8833527 33953754
    [Google Scholar]
  85. Gooding S. Leedham S.J. Gremlin 1 — small protein, big impact: the multiorgan consequences of disrupted BMP antagonism †. J. Pathol. 2020 251 4 349 352 10.1002/path.5479 32472605
    [Google Scholar]
  86. Yang W. Li H.Y. Wu Y.F. Mi R.J. Liu W.Z. Shen X. Lu Y.X. Jiang Y.H. Ma M.J. Shen H.Y. ac4C acetylation of RUNX2 catalyzed by NAT10 spurs osteogenesis of BMSCs and prevents ovariectomy-induced bone loss. Mol. Ther. Nucleic Acids 2021 26 135 147 10.1016/j.omtn.2021.06.022 34513300
    [Google Scholar]
  87. Chen C.W. Wei J.C.C. Gu J. Yu D. Editorial: Advances in Pathogenesis, Etiology, and Therapies for Ankylosing Spondylitis. Front. Immunol. 2021 12 822582 10.3389/fimmu.2021.822582 35003143
    [Google Scholar]
  88. Luo Q. Zhu J. Wang S. fu P. Fu B. Huang Z. Li J. Decreased expression of NAT10 in peripheral blood mononuclear cells from new-onset ankylosing spondylitis and its clinical significance. Arthritis Res. Ther. 2024 26 1 7 10.1186/s13075‑023‑03250‑0 38167491
    [Google Scholar]
  89. Dang Y. Li J. Li Y. Wang Y. Zhao Y. Zhao N. Li W. Zhang H. Ye C. Ma H. Zhang L. Liu H. Dong Y. Yao M. Lei Y. Xu Z. Zhang F. Ye W. N-acetyltransferase 10 regulates alphavirus replication via N4-acetylcytidine (ac4C) modification of the lymphocyte antigen six family member E (LY6E) mRNA. J. Virol. 2024 98 1 e01350-23 10.1128/jvi.01350‑23 38169284
    [Google Scholar]
  90. Ziegler U. Fischer D. Eiden M. Reuschel M. Rinder M. Müller K. Schwehn R. Schmidt V. Groschup M.H. Keller M. Sindbis virus- a wild bird associated zoonotic arbovirus circulates in Germany. Vet. Microbiol. 2019 239 108453 10.1016/j.vetmic.2019.108453 31767092
    [Google Scholar]
  91. Liao H. Ma H. Meng H. Kang N. Wang L. Ropinirole suppresses LPS-induced periodontal inflammation by inhibiting the NAT10 in an ac4C-dependent manner. BMC Oral Health 2024 24 1 510 10.1186/s12903‑024‑04250‑5 38689229
    [Google Scholar]
  92. Cui Z. Xu Y. Wu P. Lu Y. Tao Y. Zhou C. Cui R. Li J. Han R. NAT10 promotes osteogenic differentiation of periodontal ligament stem cells by regulating VEGFA-mediated PI3K/AKT signaling pathway through ac4C modification. Odontology 2023 111 4 870 882 10.1007/s10266‑023‑00793‑1 36879181
    [Google Scholar]
  93. Liu J.R. Miao H. Deng D.Q. Vaziri N.D. Li P. Zhao Y.Y. Gut microbiota-derived tryptophan metabolism mediates renal fibrosis by aryl hydrocarbon receptor signaling activation. Cell. Mol. Life Sci. 2021 78 3 909 922 10.1007/s00018‑020‑03645‑1 32965514
    [Google Scholar]
  94. Binatti E. Gerussi A. Barisani D. Invernizzi P. The Role of Macrophages in Liver Fibrosis: New Therapeutic Opportunities. Int. J. Mol. Sci. 2022 23 12 6649 10.3390/ijms23126649 35743092
    [Google Scholar]
  95. Shenshen W. Yin L. Han K. Jiang B. Meng Q. Aschner M. Li X. Chen R. NAT10 accelerates pulmonary fibrosis through N4-acetylated TGFB1-initiated epithelial-to-mesenchymal transition upon ambient fine particulate matter exposure. Environmental Pollution 2023 322 121149 10.1016/j.envpol.2023.121149
    [Google Scholar]
  96. Fabre T. Barron A.M.S. Christensen S.M. Asano S. Bound K. Lech M.P. Wadsworth M.H. II Chen X. Wang C. Wang J. McMahon J. Schlerman F. White A. Kravarik K.M. Fisher A.J. Borthwick L.A. Hart K.M. Henderson N.C. Wynn T.A. Dower K. Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation. Sci. Immunol. 2023 8 82 eadd8945 10.1126/sciimmunol.add8945 37027478
    [Google Scholar]
  97. Zi J. Han Q. Gu S. McGrath M. Kane S. Song C. Ge Z. Targeting NAT10 Induces Apoptosis Associated With Enhancing Endoplasmic Reticulum Stress in Acute Myeloid Leukemia Cells. Front. Oncol. 2020 10 598107 10.3389/fonc.2020.598107 33425753
    [Google Scholar]
  98. Cao Y. Yao M. Wu Y. Ma N. Liu H. Zhang B. N-Acetyltransferase 10 Promotes Micronuclei Formation to Activate the Senescence-Associated Secretory Phenotype Machinery in Colorectal Cancer Cells. Transl. Oncol. 2020 13 8 100783 10.1016/j.tranon.2020.100783 32428852
    [Google Scholar]
  99. Dalhat M.H. Mohammed M.R.S. Ahmad A. Khan M.I. Choudhry H. Remodelin, a N-acetyltransferase 10 (NAT10) inhibitor, alters mitochondrial lipid metabolism in cancer cells. J. Cell. Biochem. 2021 122 12 1936 1945 10.1002/jcb.30155 34605570
    [Google Scholar]
  100. Guo Q. Yu W. Tan J. Zhang J. Chen J. Rao S. Guo X. Cai K. Remodelin delays non-small cell lung cancer progression by inhibiting NAT10 via the EMT pathway. Cancer Med. 2024 13 11 e7283 10.1002/cam4.7283 38826095
    [Google Scholar]
  101. Wang C. Liu Y. Zhang Y. Wang D. Xu L. Li Z. Bai X. Wang Y. Targeting NAT10 protects against sepsis-induced skeletal muscle atrophy by inhibiting ROS/NLRP3. Life Sci. 2023 330 121948 10.1016/j.lfs.2023.121948 37467885
    [Google Scholar]
  102. Ma W. Tian Y. Shi L. Liang J. Ouyang Q. Li J. Chen H. Sun H. Ji H. Liu X. Huang W. Gao X. Jin X. Wang X. Liu Y. Yu Y. Guo X. Tian Y. Yang F. Li F. Wang N. Cai B. N-Acetyltransferase 10 represses Uqcr11 and Uqcrb independently of ac4C modification to promote heart regeneration. Nat. Commun. 2024 15 1 2137 10.1038/s41467‑024‑46458‑7 38459019
    [Google Scholar]
  103. Jiang F. Doudna J.A. CRISPR–Cas9 Structures and Mechanisms. Annu. Rev. Biophys. 2017 46 1 505 529 10.1146/annurev‑biophys‑062215‑010822 28375731
    [Google Scholar]
  104. Paddison P.J. Caudy A.A. Bernstein E. Hannon G.J. Conklin D.S. Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev. 2002 16 8 948 958 10.1101/gad.981002 11959843
    [Google Scholar]
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  • Article Type:
    Review Article
Keywords: NAT10 ; ac4C modification ; inflammatory diseases ; inflammation
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