Department of Molecular Biology, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
Department of Pediatrics and Department of Surgery, National Bohomolets Medical University, Kyiv, Ukraine.
Endocr Regul. 2023 Feb 8;57(1):37-47. doi: 10.2478/enr-2023-0005. Print 2023 Jan 1.
Homeobox genes play a fundamental role in the embryogenesis, but some of them have been linked to oncogenesis. The present study is aimed to investigate the impact of glucose and glutamine deprivations on the expression of homeobox genes such as (paired box 6), ( homeobox 3), (PBX homeobox interacting protein 1), ( homeobox 1), and in ERN1 knockdown U87 glioma cells with the intent to reveal the role of ERN1 (endoplasmic reticulum to nucleus signaling 1) signaling pathway on the endoplasmic reticulum stress dependent regulation of homeobox genes. The control (transfected by empty vector) and ERN1 knockdown (transfected by dominant-negative ERN1) U87 glioma cells were exposed to glucose and glutamine deprivations for 24 h. The cells RNA was extracted and reverse transcribed. The expression level of , , , , and genes was evaluated by a real-time quantitative polymerase chain reaction analysis and normalized to ACTB. It was found that glucose deprivation down-regulated the expression level of , , and genes in control glioma cells, but did not significantly alter and genes expression. At the same time, ERN1 knockdown significantly modified the sensitivity of all studied genes to glucose deprivation. Other changes in gene expression were detected in control glioma cells under the glutamine deprivation. The expression of and genes was down- while and genes up-regulated. Furthermore, ERN1 knockdown significantly modified the effect of glutamine deprivation on the majority of studied genes expression in U87 glioma cells. The results of the present study demonstrate that the exposure of U87 glioma cells under glucose and glutamine deprivations affected the expression of the majority of the studied homeobox genes and that the sensitivity of , , , , and genes expression under these experimental conditions is mediated by ERN1, the major pathway of the endoplasmic reticulum stress signaling.
同源盒基因在胚胎发生中起着至关重要的作用，但其中一些与肿瘤发生有关。本研究旨在探讨葡萄糖和谷氨酰胺剥夺对同源盒基因（如 （配对盒 6）、 （ homeobox 3）、 （PBX homeobox interacting protein 1）、 （ homeobox 1）和 ）表达的影响，这些基因在 ERN1（内质网到细胞核信号 1）信号通路敲低的 U87 神经胶质瘤细胞中，目的是揭示 ERN1 信号通路对内质网应激依赖的同源盒基因调节的作用。对照（转染空载体）和 ERN1 敲低（转染显性负性 ERN1）U87 神经胶质瘤细胞分别暴露于葡萄糖和谷氨酰胺剥夺 24 小时。提取细胞 RNA 并逆转录。通过实时定量聚合酶链反应分析评估 和 基因的表达水平，并与 ACTB 归一化。结果发现，葡萄糖剥夺下调对照神经胶质瘤细胞中 、 、 和 基因的表达水平，但对 基因和 基因的表达没有显著影响。同时，ERN1 敲低显著改变了所有研究基因对葡萄糖剥夺的敏感性。在对照神经胶质瘤细胞中，在谷氨酰胺剥夺下还检测到其他基因表达的变化。 和 基因的表达下调，而 基因和 基因的表达上调。此外，ERN1 敲低显著改变了 U87 神经胶质瘤细胞中谷氨酰胺剥夺对大多数研究基因表达的影响。本研究结果表明，U87 神经胶质瘤细胞在葡萄糖和谷氨酰胺剥夺下的暴露影响了大多数研究同源盒基因的表达，并且这些实验条件下 、 、 、 和 基因表达的敏感性是由 ERN1 介导的，这是内质网应激信号的主要途径。
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