High Expression of ACOT2 Predicts Worse Overall Survival and Abnormal Lipid Metabolism: A Potential Target for Acute Myeloid Leukemia.
High Expression of ACOT2 Predicts Worse Overall Survival and Abnormal Lipid Metabolism: A Potential Target for Acute Myeloid Leukemia.
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ACOT2 的高表达预示着更差的总体生存率和异常的脂质代谢：急性髓系白血病的潜在靶点
DOI：
10.1155/2022/2669114
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发表时间：
2022
影响因子：
--
通讯作者：
Xu, Ruirong
中科院分区：
文献类型：
--
作者：
Yin, Xuewei;Lyu, Chunyi;Li, Zonghong;Wang, Qian;Ding, Yi;Wang, Yan;Qiu, Yan;Cui, Siyuan;Guo, Dadong;Xu, Ruirong
酰基辅酶A硫酯酶（ACOT）在脂质代谢中发挥着重要作用，与癌症的发生和发展密切相关，但其在急性髓系白血病（AML）中的作用尚未完全阐明。为了探讨ACOT2在AML中的作用并为AML提供潜在的治疗靶点，基于TNMplot、基因表达谱交互分析（GEPIA）和癌细胞系百科全书（CCLE）数据库研究ACOT的表达模式，并基于癌症基因组图谱（TCGA）的数据探讨ACOT的诊断价值、预后价值和临床表型。通过基因本体论（GO）、京都基因和基因组百科全书（KEGG）和基因集富集分析（GSEA）分析进一步对ACOT2共表达和AML相关基因之间的共同靶标进行功能注释和富集分析。基于GeneMANIA和人类代谢组数据库构建了ACOT2共表达基因的蛋白质-蛋白质相互作用（PPI）网络和功能性ACOT2相关代谢物关联网络。根据 TNMplot、GEPIA 和 CCLE 数据库，在 ACOT 中，与正常对照受试者相比，ACOT2 在 AML 中高表达，这与 AML 较差的总生存期 (OS) 显着相关 (P=0.003)。此外，ACOT2 对 AML 表现出优异的诊断效率（AUC：1.000），并与法美英（FAB）分类和细胞遗传学相关。对ACOT2共表达与AML相关基因之间的71个共同靶点的GO、KEGG和GSEA分析表明，ACOT2与ACOT1、ACOT4、烯酰基载体蛋白还原酶、线粒体（MECR）、嘌呤霉素敏感氨肽酶（NPEPPS）、SWI/SNF相关的基质相关蛋白密切相关 PPI网络中肌动蛋白依赖性染色质亚家族B成员1（SMARCB1）和长链脂肪酸辅酶A连接酶1（ACSL1）的调节因子，在脂质代谢中发挥重要作用，即参与脂肪酸延伸和不饱和脂肪酸的生物合成。总的来说，ACOT2 的增加可能是 OS 恶化和脂质代谢异常的重要特征，表明 ACOT2 可能成为 AML 的潜在治疗靶点。
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.
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DOI：
10.3390/v14020240
发表时间：
2022-01-25
期刊：
Viruses
影响因子：
--
作者：
St Clair LA;Mills SA;Lian E;Soma PS;Nag A;Montgomery C;Ramirez G;Chotiwan N;Gullberg RC;Perera R
通讯作者：
Perera R
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
50.3
作者：
Elgendy, Mohamed;Ciro, Marco;Minucci, Saverio
通讯作者：
Minucci, Saverio
影响因子：
4.8
作者：
Hunt, MC;Solaas, K;Alexson, SEH
通讯作者：
Alexson, SEH
影响因子：
4.8
作者：
Hunt, Mary C.;Rautanen, Anna;Alexson, Stefan E. H.
通讯作者：
Alexson, Stefan E. H.