ArticleBritish journal of cancer2024
Downregulation of N4-acetylcytidine modification in myeloid cells attenuates immunotherapy and exacerbates hepatocellular carcinoma progression.
Article in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 10 citations in OpenAlex.
- ac4C modification sites prediction in human mRNA: a complete review.Briefings in bioinformatics · 2026Review
- Review
- RNA N4-acetylcytidine modification in human cancers: from molecular function to oncogenic mechanisms.iScience · 2026Review
- N4-acetylcytidine modification bridges metabolic reprogramming and immune evasion in cancer: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- mCancer cell international · 2025Article
- Targeted activation of junctional adhesion molecule-like proteinChinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- The N-acetyltransferase 10 inhibitor [EJNMMI radiopharmacy and chemistry · 2025Article
- Sophisticated roles of tumor microenvironment in resistance to immune checkpoint blockade therapy in hepatocellular carcinoma.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Targeting HCG18 counteracts ferroptosis resistance via blocking the miR-30a-5p/RRM2/GSS pathway in hepatocellular carcinoma.International journal of biological sciences · 2025Article
- The role of RNA modifications in disease-associated macrophages.Molecular therapy. Nucleic acids · 2024Review
- The role and mechanism of NAT10-mediated ac4C modification in tumor development and progression.MedComm · 2024Review
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundN4-acetylcytidine (ac4C) is a conserved and abundant mRNA modification that controls protein expression by affecting translation efficiency and mRNA stability. Whether the ac4C modification of mRNA regulates hepatocellular carcinoma (HCC) development or affects the immunotherapy of HCC is unknown.
methodsBy constructing an orthotopic transplantation mouse HCC model and isolating tumour-infiltrated immunocytes, we evaluated the ac4C modification intensity using flow cytometry. Remodelin hydrobromide (REM), an ac4C modification inhibitor, was systematically used to understand the extensive role of ac4C modification in immunocyte phenotypes. Single-cell RNA-seq was performed to comprehensively evaluate the changes in the tumour-infiltrating immunocytes and identify targeted cell clusters. RNA-seq and RIP-seq analyses were performed to elucidate the underlying molecular mechanisms. Tyramide Signal Amplification (TSA) analysis on the HCC tissue microarray was performed to explore the clinical relatedness of our findings.
resultsAc4C modification promoted M1 macrophage infiltration and reduced myeloid-derived suppressor cell MDSCs infiltration in HCC. The inhibition of ac4C modification induces PDL1 expression by stabilising mRNA in the myeloid cells, thereby attenuating the CTL-mediated tumour cell-killing ability. High infiltration of ac4C+CD11b+ cells is positively related to a better prognosis in patients with HCC.
conclusionsAc4C modification of myeloid cells enhanced the HCC immunotherapy by suppressing PDL1 expression.
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