ArticleLiver international : official journal of the International Association for the Study of the Liver2021
The biological process of lysine-tRNA charging is therapeutically targetable in liver cancer.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Protein Expression Dynamics in Breast Cancer Cells Exposed to Nano-Encapsulated Tarin, the Taro Lectin.Pharmaceutics · 2026Article
- Host mature tRNAome as a decoding switch regulates antiviral and proviral responses.Nature communications · 2026Article
- Development of tRNA-based biomarkers for breast cancer: insight from machine learning.Archives of medical science : AMS · 2026Article
- Article
- Multi-omics profiling reveals downregulated tumor lysine metabolism reshaping the immune microenvironment and therapeutic responses in hepatocellular carcinoma.Journal of translational medicine · 2025Article
- JASMINE: A powerful representation learning method for enhanced analysis of incomplete multi-omics data.bioRxiv : the preprint server for biology · 2025Article
- Quantitative proteomic analysis unveils a critical role of VARS1 in hepatocellular carcinoma aggressiveness through the modulation of MAGI1 expression.Molecular cancer · 2025Article
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- Tumor organoids for primary liver cancers: A systematic review of current applications in diagnostics, disease modeling, and drug screening.JHEP reports : innovation in hepatology · 2024Article
- Unraveling the impact of AXIN1 mutations on HCC development: Insights from CRISPR/Cas9 repaired AXIN1-mutant liver cancer cell lines.PloS one · 2024Article
- Review
- Hepatitis E virus infection remodels the mature tRNAome in macrophages to orchestrate NLRP3 inflammasome response.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Recapitulating hepatitis E virus-host interactions and facilitating antiviral drug discovery in human liver-derived organoids.Science advances · 2022Article
- Article
- L-Lysine α-Oxidase: Enzyme with Anticancer Properties.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Review
- The biological process of lysine-tRNA charging is therapeutically targetable in liver cancer.Liver international : official journal of the International Association for the Study of the Liver · 2021Article
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Authors and funding
17 authors.
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Abstract
BACKGROUND &
aimsMature transfer RNAs (tRNA) charged with amino acids decode mRNA to synthesize proteins. Dysregulation of translational machineries has a fundamental impact on cancer biology. This study aims to map the tRNAome landscape in liver cancer patients and to explore potential therapeutic targets at the interface of charging amino acid with tRNA.
methodsResected tumour and paired tumour-free (TFL) tissues from hepatocellular carcinoma (HCC) patients (n = 69), and healthy liver tissues from organ transplant donors (n = 21), HCC cell lines, and cholangiocarcinoma (CC) patient-derived tumour organoids were used.
resultsThe expression levels of different mature tRNAs were highly correlated and closely clustered within individual tissues, suggesting that different members of the tRNAome function cooperatively in protein translation. Interestingly, high expression of tRNA-Lys-CUU in HCC tumours was associated with more tumour recurrence (HR 1.1; P = .022) and worse patient survival (HR 1.1; P = .0037). The expression of Lysyl-tRNA Synthetase (KARS), the enzyme catalysing the charge of lysine to tRNA-Lys-CUU, was significantly upregulated in HCC tumour tissues compared to tumour-free liver tissues. In HCC cell lines, lysine deprivation, KARS knockdown or treatment with the KARS inhibitor cladosporin effectively inhibited overall cell growth, single cell-based colony formation and cell migration. This was mechanistically mediated by cell cycling arrest and induction of apoptosis. Finally, these inhibitory effects were confirmed in 3D cultured patient-derived CC organoids.
conclusionsThe biological process of charging tRNA-Lys-CUU with lysine sustains liver cancer cell growth and migration, and is clinically relevant in HCC patients. This process can be therapeutically targeted and represents an unexplored territory for developing novel treatment strategies against liver cancer.
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