Mitochondrial Acetyl-CoA Synthetase 3 is Biosignature of Gastric Cancer Progression
Abstract
Cholesterol affects cancer progression, and acetyl-CoA is the primary cholesterogenesis substrate. The previous work has defined cholesterol bioflux via lipoprotein/receptor route is the gastric cancer (GCa) prognosis biosignature. The prognosis importance of acetyl-CoA to cholesterogenesis (mevalonate pathway) in GCa is yet to be defined. Using Kaplan-Meier Plotter web-based gene survival analyzer and The Cancer Genome Atlas (TCGA)-database analyzed with DBdriver.v2 platform, we revealed acetyl-CoA production and the mevalonate pathway are associated with GCa prognosis. We found mitochondrial-derived acetyl-CoA contributing enzymes (acyl-coA synthetase super-family 3; ACSS3) is the GCa progression confounder. Interestingly, it is not HMGCR (the committee enzyme of mevalonate pathway), but lower mevalonate pathway enzymes (e.g., MVK, LSS, DHCR14A1, SC4MOL, HSD17B7, SC5D) promote GCa patients 5-years overall survival in a differential level. Advanced analyses found ACSS3 is prognosis biosignatures for multiple GCa disease conditions. This report uncovered a higher expression of ACSS3 in tumor comparing to normal parental lesions, which implicates a targeting value for GCa therapy. While knockdown ACSS3 could suppress growth and ...Continue Reading
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