Effect of aryl hydrocarbon receptor gene knockout on metabolic pathways and metabolites in hepatocellular carcinoma

Abstract

Abstract: Objective:To investigate the effect of aryl hydrocarbon receptor (AHR) gene knockout on metabolic pathways and metabolites in hepatocellular carcinoma (HCC). Method:PLC/PRF/5 hepatoma cell line with AHR knockout was constructed by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. Untargeted metabolomics was performed on the wild type (AHR-WT) and AHR knockout (AHR-KO) hepatoma cells to detect the metabolites, and the differential metabolites between the two groups were analyzed. Metaboanalyst 4.0 was used to perform metabolic pathway enrichment analysis and find differential metabolites.
Result:The AHR-WT and AHR-KO hepatoma cells were examined for metabolites under positive and negative ionic model respectively. The results showed that the top 10 functional enrichments were mainly amino acid metabolism glutamate metabolism, glycine and serine metabolism, arginine and proline metabolism, methionine metabolism, aspartate metabolism, urea cycle, ammonia recycling, energy metabolism glutathione metabolism, Warburg effect and nucleotide metabolism purine metabolism. The pathway enrichment analysis showed that eight metabolic pathways were found including arginine and proline metabolism, arginine biosynthesis, pyrimidine metabolism, alanine, aspartic acid and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, purine metabolism, lysine degradation, ascorbic acid and uronate metabolism. Compared with AHR-WT hepatoma cells, the levels of L-arginine, L-phenylalanine, L-tyrosine, uridine and xanthine were significantly down-regulated in AHR-KO hepatoma cells. Nicotinamide adenine dinucleotide (NADH), oxidized glutathione and nicotinamide adenine dinucleotide phosphate (NADPH) were significantly up-regulated in the AHR-KO cells. Conclusion:AHR may play an important role in the metabolism of HCC, and the research on the metabonomics of HCC by targeting AHR may be a new anti-tumor treatment strategy.

Key words: Hepatocellular carcinoma, Aryl hydrocarbon receptor, Metabolomics

Wei Zhewen, Zhu Qing, Cai Jianqiang. Effect of aryl hydrocarbon receptor gene knockout on metabolic pathways and metabolites in hepatocellular carcinoma[J]. Electronic Journal of Liver Tumor, 2023, 10(4): 23-28.

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