High Expression of ACOT2 Predicts Worse Overall Survival and Abnormal Lipid Metabolism: A Potential Target for Acute Myeloid Leukemia

Abstract

Acyl-CoA thioesterase (ACOT) plays a considerable role in lipid metabolism, which is closely related to the occurrence and development of cancer, nevertheless, its role has not been fully elucidated in acute myeloid leukemia (AML). To explore the role of ACOT2 in AML and to provide a potential therapeutic target for AML, the expression pattern of ACOT was investigated based on the TNMplot, Gene Expression Profiling Interactive Analysis (GEPIA), and Cancer Cell Line Encyclopedia (CCLE) database, and diagnostic value, prognostic value, and clinical phenotype of ACOT were explored based on data from The Cancer Genome Atlas (TCGA). Functional annotation and enrichment analysis of the common targets between ACOT2 coexpressed and AML-related genes were further performed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses. The protein-protein interaction (PPI) network of ACOT2 coexpressed genes and functional ACOT2-related metabolites association network were constructed based on GeneMANIA and Human Metabolome Database. Among ACOTs, ACOT2 was highly expressed in AML compared to normal control subjects according to TNMplot, GEPIA, and CCLE database, which was significantly associated with poor overall survival (OS) in AML ( P = 0.003 ). Moreover, ACOT2 exhibited excellent diagnostic efficiency for AML (AUC: 1.000) and related to French-American-British (FAB) classification and cytogenetics. GO, KEGG, and GSEA analyses of 71 common targets between ACOT2 coexpressed and AML-related genes revealed that ACOT2 is closely related to ACOT1, ACOT4, enoyl-acyl carrier protein reductase, mitochondrial (MECR), puromycin-sensitive aminopeptidase (NPEPPS), SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and long-chain fatty acid-CoA ligase 1 (ACSL1) in PPI network, and plays a significant role in lipid metabolism, that is, involved in fatty acid elongation and biosynthesis of unsaturated fatty acids. Collectively, the increase of ACOT2 may be an important characteristic of worse OS and abnormal lipid metabolism, suggesting that ACOT2 may become a potential therapeutic target for AML.

Human umbilical cord mesenchymal stem cells attenuate diet-induced obesity and NASH-related fibrosis in mice

“…5 B). Several other studies have demonstrated that Acot1 , Acot2 , Acot3 , Cyp4a10 , and Cyp4a14 are closely related to steatosis, inflammation, and liver fibrosis [ [23] , [24] , [25] , [26] , [27] , [28] ]. Thus, Acot1 , Cyp4a10 , and Cyp4a14 were selected for further validation by qPCR in the livers of both groups, with the expression of all three genes decreasing significantly in the hUC-MSC-treated group ( Fig.…”

“…Overexpression of Acot2 in the liver leads to increased oxidation of fatty acids in vivo. Recently, some researchers have predicted that an increase in Acot2 expression may be an important feature of abnormal lipid metabolism [ 25 ]. Another study indicated that high fructose corn syrup consumption significantly increases Acot2 and Acot3 expression in mice [ 26 ].…”

Progress of the acyl-Coenzyme A thioester hydrolase family in cancer

“…In acute myeloid leukemia (AML) of the blood system ( 49 , 50 ), ACOT 2 and ACOT 7 plays an important role in lipid metabolism such as fatty acid elongation and the biosynthesis of unsaturated fatty acids. Among them, ACOT 2 was up-regulated in AML cell lines, and its high expression predicted decreased overall survival and abnormal lipid metabolism during disease progression in AML.…”