关键词: 全基因组规模代谢模型, 肝细胞肝癌, 基因敲除, 胆固醇合成, L-氯化棕榈酰肉碱

Abstract: Since the altered metabolism is the most significant characteristic in tumor cells, cancer can also be regarded as a kind of complex metabolic diseases.At the meantime, genome-scale metabolic models have appeared as a growing success in exploring mechanism of various metabolic diseases as well as identifying potential therapeutic targets, including several cancers. By comparing the metabolism difference of hepatocellular carcinoma (HCC) tumor cell and normal liver cell, we found that AKG plays an important role in regulating tumor growth, so it can be targeted in cancer treatment, while the altered catalytic mechanismin HCC tumor cells indicated that TECR might be the potential anti-tumor gene. Furthermore, several key metabolic reprogramming processes have taken place in cholesterol biosynthesis pathway. In addition, the depletion of DHCR24 and HMGCS2 can help tumor cells avoid apoptosis, which have been experimentally proved by previous study; the presence of IDI2 may contribute to improving cell proliferation and the ability of invasion and migration. We also found that intermediate products in choline metabolism are able to accelerate cancer progression by enhancing pro-inflammatory pathways through fatty acids biosynthesis. To conclude, lethal genes and synthetic lethal gene pairs identified in this study have important influences on tumor cell growth, and they can be potential targets for further clinical treatment.

Key words: genome-scale metabolic model, hepatocellular carcinoma, gene deletion, cholesterol biosynthesis, L-palmitoylcarnitine