ArticleCancer communications (London, England)2024
Targeting N4-acetylcytidine suppresses hepatocellular carcinoma progression by repressing eEF2-mediated HMGB2 mRNA translation.
Article in Cancer communications (London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Predictive and clinicopathological importance of HMGB2 in various carcinomas: a meta and bioinformatic approach.Scientific reports · 2025Pooled it
- RNA N4-acetylcytidine modification in health and cancer: molecular mechanisms, cellular plasticity, and therapeutic opportunities.Biomarker research · 2026Review
- DUSP12 Regulates NAT10-Mediated RNA Acetylation to Modulate DNA Repair and Therapeutic Response in Hepatocellular Carcinoma.MedComm · 2026Article
- The RNA helicase domain of NAT10 promotes the biogenesis of hypomodified ribosomes to enhance cancer cell proliferation.Nature communications · 2026Article
- Targeting NAT10 Activates Tumor-Intrinsic Immunity and Suppresses Tumor Progression in Head and Neck Squamous Cell Carcinoma.bioRxiv : the preprint server for biology · 2026Article
- The functions, mechanisms and clinical relevance of RNA and protein acetyltransferase NAT10: a comprehensive review.Cell biology and toxicology · 2026Review
- Cuproptosis and Mitophagy Mediated by the THUMPD1/IGF2R-Dependent Suppression of AKT and Activation of AMPK Signaling Suppress Lung Adenocarcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Depletion of NAT10 in T cells attenuates metabolic dysfunction-associated steatohepatitis in mice.Hepatology communications · 2026Article
- NAT10 inhibition alleviates renal tubular epithelial cell senescence by impeding ac4C acetylation of PAPP-A mRNA in diabetic nephropathy.Cell death & disease · 2026Article
- NAT10 promotes the activation of hepatic stellate cells by modulating the TGF-β1-ac4C-COL1A1 axis.Hepatology international · 2026Article
- NAT10/acProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Integrative interpretable learning reveals shared patterns of epitranscriptomic regulation across multiple cancer types.BMC biology · 2026Article
- ac4C modification sites prediction in human mRNA: a complete review.Briefings in bioinformatics · 2026Review
- Review
- NAT10 promotes cisplatin resistance and immune escape by increasing the expression of DUSP1 and PD-L1 in gastric cancer.Cell death discovery · 2026Article
- RNA N4-acetylcytidine modification in human cancers: from molecular function to oncogenic mechanisms.iScience · 2026Review
- NAT10-mediated ac4C RNA acetylation stabilizes CXCL5/DEK mRNA to drive proliferation and metastasis in lung adenocarcinoma.Cell death & disease · 2026Article
- Integrated epigenetic networks in aging: from histone to RNA modifications.Journal of translational medicine · 2026Review
- The NAT10/acCell communication and signaling : CCS · 2026Review
- Targeting NAT10 alleviates colonic senescence and elderly-onset colitis by disrupting N4-acetylation of DYRK1A.Nature communications · 2026Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
backgroundN4-acetylcytidine (ac4C) represents a novel messenger RNA (mRNA) modification, and its associated acetyltransferase N-acetyltransferase 10 (NAT10) plays a crucial role in the initiation and progression of tumors by regulating mRNA functionality. However, its role in hepatocellular carcinoma (HCC) development and prognosis is largely unknown. This study aimed to elucidate the role of NAT10-mediated ac4C in HCC progression and provide a promising therapeutic approach.
methodsThe ac4C levels were evaluated by dot blot and ultra-performance liquid chromatography-tandem mass spectrometry with harvested HCC tissues. The expression of NAT10 was investigated using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemical staining across 91 cohorts of HCC patients. To explore the underlying mechanisms of NAT10-ac4C in HCC, we employed a comprehensive approach integrating acetylated RNA immunoprecipitation and sequencing, RNA sequencing and ribosome profiling analyses, along with RNA immunoprecipitation, RNA pull-down, mass spectrometry, and site-specific mutation analyses. The drug affinity responsive targets stability, cellular thermal shift assay, and surface plasmon resonance assays were performed to assess the specific binding of NAT10 and Panobinostat. Furthermore, the efficacy of targeting NAT10-ac4C for HCC treatment was elucidated through in vitro experiments using HCC cells and in vivo HCC mouse models.
resultsOur investigation revealed a significant increase in both the ac4C RNA level and NAT10 expression in HCC. Notably, elevated NAT10 expression was associated with poor outcomes in HCC patients. Functionally, silencing NAT10 suppressed HCC proliferation and metastasis in vitro and in vivo. Mechanistically, NAT10 stimulates the ac4C modification within the coding sequence (CDS) of high mobility group protein B2 (HMGB2), which subsequently enhances HMGB2 translation by facilitating eukaryotic elongation factor 2 (eEF2) binding to the ac4C sites on HMGB2 mRNA's CDS. Additionally, high-throughput compound library screening revealed Panobinostat as a potent inhibitor of NAT10-mediated ac4C modification. This inhibition significantly attenuated HCC growth and metastasis in both in vitro experiments using HCC cells and in vivo HCC mouse models.
conclusionsOur study identified a novel oncogenic epi-transcriptome axis involving NAT10-ac4C/eEF2-HMGB2, which plays a pivotal role in regulating HCC growth and metastasis. The drug Panobinostat validates the therapeutic potential of targeting this axis for HCC treatment.
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