This study plans to investigate the effects of long-noncoding RNA MACC1-AS1 on glioma cells and its mechanism at metabolic plasticity angle. The MACC1-AS1 level was identified both in glioma tissues and in cells. Then the effects of MACC1-AS1 abnormal level on cell viability, apoptosis, the expression of apoptosis associated protein, glucose metabolism and redox status were measured in A172 and U251 cells by different methods. Furthermore, the interaction of MACC1-AS1 and MACC1 in glioma cells was investigated and the role of AMPK pathway was specifically examined. Our results demonstrated that MACC1-AS1 level was high in glioma tissues and cells, and MACC1-AS1 overexpression was closely associated with poor prognosis of glioma. Notably, under glucose deprivation, the MACC1-AS1 level was significantly increased, and overexpression of MACC1-AS1 increased cell viability but inhibited apoptosis. Also, MACC1-AS1 overexpression obviously increased the levels of GLUT1, HK2, G6PD, MCT1, ATP, lactate and NAPDH as well as promoted the activities of HK2 and LDHA, while reduced ROS level and the ratio of NADP+/NAPDH. In particular, the effects of proliferation, apoptosis and metabolic plasticity of glioma cells caused by MACC1-AS1 overexpression were achieved by positively regulating MACC1, and MACC1-AS1 promoted MACC1 expression via the AMPK pathway. In conclusions, the MACC1-AS1/MACC1 axis exertes the tumor-promoting effect by regulating glucose metabolism and redox homeostasis in glioma cells by activating the AMPK signals.

本研究拟从代谢可塑性角度探讨长链非编码RNA MACC1-AS1对胶质瘤细胞的影响及其机制。MACC1-AS1 水平在神经胶质瘤组织和细胞中均被鉴定。然后通过不同方法测定MACC1-AS1异常水平对A172和U251细胞活力、凋亡、凋亡相关蛋白表达、糖代谢和氧化还原状态的影响。此外，研究了胶质瘤细胞中 MACC1-AS1 和 MACC1 的相互作用，并特别检查了 AMPK 通路的作用。我们的研究结果表明，胶质瘤组织和细胞中 MACC1-AS1 水平较高，MACC1-AS1 过表达与胶质瘤预后不良密切相关。值得注意的是，在葡萄糖剥夺下，MACC1-AS1 水平显着增加，MACC1-AS1 的过表达增加了细胞活力但抑制了细胞凋亡。此外，MACC1-AS1过表达明显增加了GLUT1、HK2、G6PD、MCT1、ATP、乳酸和NAPDH的水平，促进了HK2和LDHA的活性，同时降低了ROS水平和NADP+/NAPDH的比例。特别是MACC1-AS1过表达引起的胶质瘤细胞增殖、凋亡和代谢可塑性的作用是通过正向调控MACC1来实现的，MACC1-AS1通过AMPK通路促进MACC1的表达。总之，MACC1-AS1/MACC1轴通过激活AMPK信号来调节胶质瘤细胞的葡萄糖代谢和氧化还原稳态，从而发挥促癌作用。乳酸和 NAPDH 以及促进 HK2 和 LDHA 的活性，同时降低 ROS 水平和 NADP+/NAPDH 的比率。特别是MACC1-AS1过表达引起的胶质瘤细胞增殖、凋亡和代谢可塑性的作用是通过正向调控MACC1来实现的，MACC1-AS1通过AMPK通路促进MACC1的表达。总之，MACC1-AS1/MACC1轴通过激活AMPK信号来调节胶质瘤细胞的葡萄糖代谢和氧化还原稳态，从而发挥促癌作用。乳酸和 NAPDH 以及促进 HK2 和 LDHA 的活性，同时降低 ROS 水平和 NADP+/NAPDH 的比率。特别是MACC1-AS1过表达引起的胶质瘤细胞增殖、凋亡和代谢可塑性的作用是通过正向调控MACC1来实现的，MACC1-AS1通过AMPK通路促进MACC1的表达。总之，MACC1-AS1/MACC1轴通过激活AMPK信号来调节胶质瘤细胞的葡萄糖代谢和氧化还原稳态，从而发挥促癌作用。MACC1-AS1 通过 AMPK 通路促进 MACC1 表达。总之，MACC1-AS1/MACC1轴通过激活AMPK信号来调节胶质瘤细胞的葡萄糖代谢和氧化还原稳态，从而发挥促癌作用。MACC1-AS1 通过 AMPK 通路促进 MACC1 表达。总之，MACC1-AS1/MACC1轴通过激活AMPK信号来调节胶质瘤细胞的葡萄糖代谢和氧化还原稳态，从而发挥促癌作用。