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Integrated Metabolomics and Lipidomics Analyses Reveal Metabolic Reprogramming in Human Glioma with IDH1 Mutation.
Journal of Proteome Research ( IF 4.4 ) Pub Date : 2019-01-09 , DOI: 10.1021/acs.jproteome.8b00663
Lina Zhou 1 , Zhichao Wang 1, 2 , Chunxiu Hu 1 , Chaoqi Zhang 3 , Petia Kovatcheva-Datchary 1 , Di Yu 1, 2 , Shasha Liu 3 , Feifei Ren 3 , Xiaolin Wang 1 , Yanli Li 1 , Xiaoli Hou 1 , Hailong Piao 1 , Xin Lu 1 , Yi Zhang 3 , Guowang Xu 1
Affiliation  

Mutations in isocitrate dehydrogenase ( IDH) 1 are high-frequency events in low-grade glioma and secondary glioblastoma, and IDH1 mutant gliomas are vulnerable to interventions. Metabolic reprogramming is a hallmark of cancer. In this study, comprehensive metabolism investigation of clinical IDH1 mutant glioma specimens was performed to explore its specific metabolic reprogramming in real microenvironment. Massive metabolic alterations from glycolysis to lipid metabolism were identified in the IDH1 mutant glioma tissue when compared to IDH1 wild-type glioma. Of note, tricarboxylic acid (TCA) cycle intermediates were in similar levels in both groups, with more pyruvate found entering the TCA cycle in IDH1 mutant glioma. The pool of fatty acyl chains was also reduced, displayed as decreased triglycerides and sphingolipids, although membrane phosphatidyl lipids were not changed. The lower fatty acyl pool may be mediated by the lower protein expression levels of long-chain acyl-CoA synthetase 1 (ACSL1), ACSL4, and very long-chain acyl-CoA synthetase 3 (ACSVL3) in IDH1 mutant glioma. Lower ACSL1 was further found to contribute to the better survival of IDH1 mutant glioma patients based on the The Cancer Genome Atlas (TCGA) RNA sequencing data. Our research provides valuable insights into the tissue metabolism of human IDH1 mutant glioma and unravels new lipid-related targets.

中文翻译:

集成的代谢组学和脂质组学分析揭示了具有IDH1突变的人胶质瘤的代谢重编程。

在低级神经胶质瘤和继发性胶质母细胞瘤中,异柠檬酸脱氢酶(IDH)1的突变是高频事件,而IDH1突变型神经胶质瘤易受干预。代谢重编程是癌症的标志。在这项研究中,对临床IDH1突变型神经胶质瘤标本进行了全面的代谢研究,以探索其在真实微环境中的特定代谢重编程。与IDH1野生型神经胶质瘤相比,IDH1突变神经胶质瘤组织中发现了从糖酵解到脂质代谢的大量代谢变化。值得注意的是,两组中的三羧酸(TCA)循环中间体含量相似,在IDH1突变型神经胶质瘤中,有更多的丙酮酸进入TCA循环。脂肪酰基链的集合也减少了,表现为甘油三酯和鞘脂减少,尽管膜磷脂酰脂质没有改变。较低的脂肪酰基池可能由IDH1突变型神经胶质瘤中长链酰基辅酶A合成酶1(ACSL1),ACSL4和长链酰基辅酶A合成酶3(ACSVL3)的较低蛋白表达水平介导。根据癌症基因组图谱(TCGA)RNA测序数据,还发现较低的ACSL1有助于IDH1突变神经胶质瘤患者的更好生存。我们的研究为人类IDH1突变型神经胶质瘤的组织代谢提供了宝贵的见识,并揭示了新的脂质相关靶标。根据癌症基因组图谱(TCGA)RNA测序数据,还发现较低的ACSL1有助于IDH1突变神经胶质瘤患者的更好生存。我们的研究为人类IDH1突变型神经胶质瘤的组织代谢提供了宝贵的见识,并阐明了新的脂质相关靶标。根据癌症基因组图谱(TCGA)RNA测序数据,还发现较低的ACSL1有助于IDH1突变神经胶质瘤患者的更好生存。我们的研究为人类IDH1突变型神经胶质瘤的组织代谢提供了宝贵的见识,并阐明了新的脂质相关靶标。
更新日期:2019-02-07
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