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周期蛋白 G2 通过抑制脑胶质瘤中 LDHA 的磷酸化抑制瓦博格效应和肿瘤进展。

Cyclin G2 Inhibits the Warburg Effect and Tumour Progression by Suppressing LDHA Phosphorylation in Glioma.

机构信息

The Research Center for Medical Genomics, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.

出版信息

Int J Biol Sci. 2019 Jan 1;15(3):544-555. doi: 10.7150/ijbs.30297. eCollection 2019.

Abstract

Cyclin G2 has been identified as a tumour suppressor in several cancers. However, its regulatory roles and underlying mechanisms in tumours are still unknown. In this study, we demonstrated that cyclin G2 was expressed at low levels in glioma, which was as a poor prognostic factor for this disease. We also found that, cyclin G2 could suppress cell proliferation, initiate cell apoptosis and reduce aerobic glycolysis, suggesting that cyclin G2 plays a tumour suppressive role in glioma. Mechanistically, cyclin G2 could negatively regulate tyrosine-10 phosphorylation of a critical glycolytic enzyme, lactate dehydrogenase A, through direct interaction. Taken together, these results indicate that cyclin G2 acts as a tumour suppressor in glioma by repressing glycolysis and tumour progression through its interaction with LDHA.

摘要

周期蛋白 G2 在几种癌症中被鉴定为肿瘤抑制因子。然而,其在肿瘤中的调节作用和潜在机制尚不清楚。在这项研究中,我们表明,周期蛋白 G2 在神经胶质瘤中表达水平较低,这是该疾病的预后不良因素。我们还发现,周期蛋白 G2 可以抑制细胞增殖,启动细胞凋亡,减少有氧糖酵解,表明周期蛋白 G2 在神经胶质瘤中发挥肿瘤抑制作用。从机制上讲,周期蛋白 G2 可以通过直接相互作用负调控关键糖酵解酶乳酸脱氢酶 A 的酪氨酸-10 磷酸化。综上所述,这些结果表明,周期蛋白 G2 通过与 LDHA 的相互作用抑制糖酵解和肿瘤进展,在神经胶质瘤中发挥肿瘤抑制作用。

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