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ALKBH5 Promotes the Proliferation of Glioma Cells via Enhancing the mRNA Stability of G6PD
Neurochemical Research ( IF 3.7 ) Pub Date : 2021-07-23 , DOI: 10.1007/s11064-021-03408-9
Zhifeng Liu 1 , Yonghan Chen 1 , Leilei Wang 1 , Suzhen Ji 2
Affiliation  

This study aims to investigate the biological role of 6-methyladenine (m6A) methylation in inducing the carcinogenesis of glioma and its proliferation. Relative levels of ALKBH5 and glucose-6-phosphate dehydrogenase (G6PD) in glioma tissues and cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Gain-of-function and loss-of-function approaches were used to investigate the role of ALKBH5 in mediating proliferation and energy metabolism of glioma cells. The regulatory effect of ALKBH5 on G6PD was analyzed using m6A-qRT-PCR. Our results showed that ALKBH5 was upregulated in glioma, which stimulated glioma cells to proliferate. Serving as a m6A eraser, ALKBH5 demethylated the target transcript G6PD and enhanced its mRNA stability, thereby promoting G6PD translation and activating the pentose phosphate pathway (PPP). Collectively, ALKBH5 stimulates glioma cells to proliferate through erasing the m6A methylation of G6PD, which can be utilized as a potential therapeutic target for glioma.



中文翻译:

ALKBH5通过增强G6PD mRNA稳定性促进胶质瘤细胞增殖

本研究旨在探讨 6-甲基腺嘌呤 (m6A) 甲基化在诱导胶质瘤癌变及其增殖中的生物学作用。通过定量实时聚合酶链反应 (qRT-PCR) 和蛋白质印迹测定胶质瘤组织和细胞系中 ALKBH5 和葡萄糖 6-磷酸脱氢酶 (G6PD) 的相对水平。功能获得和功能丧失方法用于研究 ALKBH5 在介导胶质瘤细胞增殖和能量代谢中的作用。使用 m6A-qRT-PCR 分析 ALKBH5 对 G6PD 的调节作用。我们的研究结果表明,ALKBH5 在胶质瘤中上调,刺激胶质瘤细胞增殖。作为 m6A 擦除器,ALKBH5 使靶转录物 G6PD 去甲基化并增强其 mRNA 稳定性,从而促进 G6PD 翻译并激活戊糖磷酸途径 (PPP)。总的来说,ALKBH5 通过消除 G6PD 的 m6A 甲基化来刺激胶质瘤细胞增殖,这可用作胶质瘤的潜在治疗靶点。

更新日期:2021-07-23
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