Department of Neurosurgery, Cangzhou Central Hospital, No. 16, Xinhua West Road, Cangzhou, 061001, Hebei, China.
Department of Emergency, Cangzhou Central Hospital, Cangzhou, China.
Neurochem Res. 2021 Nov;46(11):3003-3011. doi: 10.1007/s11064-021-03408-9. Epub 2021 Jul 23.
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.
本研究旨在探讨 6-甲基腺嘌呤（m6A）甲基化在诱导神经胶质瘤发生和增殖中的生物学作用。通过实时定量聚合酶链反应（qRT-PCR）和 Western blot 测定神经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。采用功能获得和功能丧失方法研究 ALKBH5 在介导神经胶质瘤细胞增殖和能量代谢中的作用。通过 m6A-qRT-PCR 分析 ALKBH5 对 G6PD 的调节作用。我们的结果表明，ALKBH5 在神经胶质瘤中上调，刺激神经胶质瘤细胞增殖。作为一种 m6A 去甲基化酶，ALKBH5 去甲基化靶转录本 G6PD 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）。总之，ALKBH5 通过去除 G6PD 的 m6A 甲基化来刺激神经胶质瘤细胞增殖，可作为神经胶质瘤的潜在治疗靶点。
