Abstract
Purpose
Lipoyltransferase 1 (LIPT1) has been recently identified as a cuproptosis‑related gene. As a key enzyme of lipoic acid metabolism, LIPT1 has been revealed to play important roles in hereditary diseases involved with lipoic acid biosynthesis defects, while its roles in hepatocellular carcinoma (HCC) remain to be elucidated. Hence, we aimed to explore the roles and mechanisms of LIPT1 in HCC progression.
Methods
The expression of LIPT1 in HCC tissues and its clinical significance for HCC were evaluated by bioinformatic analysis and in our patient cohort. The influences of LIPT1 on the growth, migration, and lipid metabolism of HCC cells were assessed in vitro. The underlying mechanisms were explored using gene set enrichment analysis (GSEA) and molecular experiments.
Results
LIPT1 expression was significantly elevated in HCC tissues compared to the normal tissues, and such upregulation was associated with more malignant pathological features and poor prognosis of patients with HCC. LIPT1 silencing significantly inhibited cell proliferation, migration, and lipid content. GSEA revealed that LIPT1 upregulation was significantly associated with various cancer-associated signaling pathways, including the PI3K-AKT signaling pathway and the Wnt/β-catenin pathway. Further molecular experiments indicated that LIPT1 silencing repressed the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and inactivated the AKT/GSK-3β/β-catenin signaling axis.
Conclusions
Upregulation of LIPT1 is involved in metabolic dysregulation of fatty acid and poor prognosis of HCC patients, which suggests that LIPT1 plays an important role in reprogramming lipid metabolism and could act as a potential prognostic marker and therapeutic target for HCC.
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Availability of data and materials
The datasets used in the current study are available in the following repositories, GEO database (https://www.ncbi.nlm.nih.gov/geo/), HPA RNA-seq normal tissues (https://www.ncbi.nlm.nih.gov/gene/51601), and TCGA database (https://portal.gdc.cancer.gov/).
Abbreviations
- AFP:
-
Alpha-fetoprotein
- CI:
-
Confidence interval
- DSS:
-
Disease special survival
- GEO:
-
Gene Expression Omnibus
- GSEA:
-
Gene set enrichment analysis
- HCC:
-
Hepatocellular carcinoma
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- LIPT1:
-
Lipoyltransferase 1
- NES:
-
Normalized Enrichment Score
- OS:
-
Overall survival
- PFI:
-
Progress-free interval
- ROC:
-
Receiver operating characteristic
- TCGA:
-
The Cancer Genome Atlas
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Acknowledgements
All authors thank the GEO and TCGA databases for providing the useful data, and all the bioinformatics tools for data analysis, and thank the Xiantao bioinformatics toolbox (https://www.xiantao.love/products) for its help in analyzing the relationship between LIPT1 expression and patients’ clinical parameters.
Funding
This work was supported in part by the National Natural Science Foundation of China (82160590 and 81802884), and The innovative project of Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, and the Special funding for 2019 Guangxi BaGui Scholars.
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Conception and design: JG and JL. Acquisition of Data: JL, DT and GG. Performing the experiment: DT and JL. Analysis and interpretation of data: JL, JG, and GG. Writing the manuscript: JL and JG. All authors contributed to the article and approved the submitted version.
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Li, J., Tuo, D., Guo, G. et al. Aberrant expression of cuproptosis‑related gene LIPT1 is associated with metabolic dysregulation of fatty acid and prognosis in hepatocellular carcinoma. J Cancer Res Clin Oncol 149, 15763–15779 (2023). https://doi.org/10.1007/s00432-023-05325-6
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DOI: https://doi.org/10.1007/s00432-023-05325-6