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首页> 外文期刊>Molecular medicine reports >Overexpression of isocitrate dehydrogenase-1(R132H) enhances the proliferation of A172 glioma cells via aerobic glycolysis
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Overexpression of isocitrate dehydrogenase-1(R132H) enhances the proliferation of A172 glioma cells via aerobic glycolysis

机译：过量表达异柠檬酸脱氢酶-1（R132H）通过有氧糖酵解增强A172胶质瘤细胞的增殖

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摘要

Gliomas are the most common type of primary malignancy of the central nervous system. The identification of mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) represents a key area of investigation in studies on glioma. The IDH1(R132H) mutation is a heterozygous point mutation, which affects the amino acid arginine at position 132, however, the metabolic importance of this mutation in tumor cell growth remains to be elucidated. In the present study, A172 glioma cell lines stably overexpressing either wild-type IDH1 or IDH1(R132H) were produced. The results demonstrated that the IDH1(R132H) mutation enhanced the proliferation of the A172 glioma cells in vitro. Furthermore, IDH1(R132H) performed this function by elevating the expression levels of hypoxia inducible factor-la, leading to an increase in the expression levels of the key glycolytic enzymes, glucose transporter 1 and hexokinase 2. Therefore, the metabolism was shifted towards aerobic glycolysis, leading to an increase in glucose uptake and lactate production. These findings demonstrated that the IDH1(R132H) molecular target was involved in orchestrating the Warburg effect in mutant IDH1(R132H) glioma cells.
机译：神经胶质瘤是中枢神经系统最常见的原发性恶性肿瘤。鉴定异柠檬酸脱氢酶-1（IDH1）编码基因中的突变是神经胶质瘤研究中的关键研究领域。 IDH1（R132H）突变是杂合点突变，会影响位置132处的氨基酸精氨酸，但是，该突变在肿瘤细胞生长中的代谢重要性尚待阐明。在本研究中，产生稳定过表达野生型IDH1或IDH1（R132H）的A172胶质瘤细胞系。结果表明，IDH1（R132H）突变增强了A172胶质瘤细胞的体外增殖。此外，IDH1（R132H）通过提高缺氧诱导因子-1a的表达水平来执行此功能，从而导致关键糖酵解酶，葡萄糖转运蛋白1和己糖激酶2的表达水平增加。因此，新陈代谢向有氧运动转移糖酵解，导致葡萄糖摄取和乳酸产生增加。这些发现表明，IDH1（R132H）分子靶标参与了突变IDH1（R132H）胶质瘤细胞的Warburg效应的编排。

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