Affiliation:
1. GIST
2. Gwangju Institute of Science and Technology
Abstract
Abstract
Gastrointestinal malignancies such as colon adenocarcinoma (COAD) and liver hepatocellular carcinoma (LIHC) are the major causes of cancer-related deaths worldwide. Identifying the common genetic foundations and signaling pathways among these cancers can lead to improved understanding of their underlying mechanisms and potential therapeutic targets. Here, we tried to identify differentially expressed genes (DEGs) and enriched pathways associated with tumorigenesis using publicly accessible the Cancer Genome Atlas datasets of COAD and LIHC. Our analysis revealed that DEGs during early tumorigenesis were associated with various aspects of cell cycle regulation. Genes related to lipid metabolism were significantly enriched in COAD and LIHC, suggesting that dysregulated lipid metabolism may play a crucial role in the development and progression of COAD and LIHC. A subset of DEGs associated with mitochondrial function and structure was identified, among which genes involved in mitochondrial protein import and mitochondrial respiratory complex assembly were upregulated in both cancers. We identified mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) as a crucial regulator of cancer cell metabolism. Using a genome-scale metabolic model, we showed that HMGCS2 suppression increased glycolysis, lipid biosynthesis and elongation, and decreased fatty acid oxidation in colon cancer cells. Overall, the present study highlights the potential contribution of dysregulated lipid metabolism, including ketogenesis, to the development and progression of COAD and LIHC. These findings could prove vital for developing targeted therapies for these malignancies and pave the way for more effective treatments.
Publisher
Research Square Platform LLC
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