Department of Radiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.
Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, China.
PLoS One. 2023 Sep 1;18(9):e0291092. doi: 10.1371/journal.pone.0291092. eCollection 2023.
Astrocyte elevated gene-1 (AEG-1) is an important oncogene that overexpresses in gliomas and plays a vital role in their occurrence and progression. However, few reports have shown which biomarkers could reflect the level of AEG-1 expression in vivo so far. In recent years, intracellular metabolites monitored by proton magnetic resonance spectroscopy (1H MRS) as non-invasive imaging biomarkers have been applied to the precise diagnosis and therapy feedback of gliomas. Therefore, understanding the correlation between 1H MRS metabolites and AEG-1 gene expression in U251 cells may help to identify relevant biomarkers. This study constructed three monoclonal AEG-1-knockout U251 cell lines using the clustered regularly interspaced short palindromic repeat (CRISPR) /Cas9 technique and evaluated the biological behaviors and metabolite ratios of these cell lines. With the decline in AEG-1 expression, the apoptosis rate of the AEG-1-knockout cell lines increased. At the same time, the metastatic capacities decreased, and the relative contents of total choline (tCho) and lactate (Lac) were also reduced. In conclusion, deviations in AEG-1 expression influence the apoptosis rate and metastasis capacity of U251 cells, which the 1H MRS metabolite ratio could monitor. The tCho/creatinine(Cr) and Lac/Cr ratios positively correlated with the AEG-1 expression and malignant cell behavior. This study may provide potential biomarkers for accurate preoperative diagnosis and future AEG-1-targeting treatment evaluation of gliomas in vivo.
星形细胞上调基因-1（AEG-1）是一种在神经胶质瘤中过度表达的重要癌基因，在其发生和发展中起着至关重要的作用。然而，到目前为止，很少有报道表明哪些生物标志物可以反映体内 AEG-1 的表达水平。近年来，质子磁共振波谱（1H MRS）监测的细胞内代谢物作为非侵入性成像生物标志物已应用于神经胶质瘤的精确诊断和治疗反馈。因此，了解 1H MRS 代谢物与 U251 细胞中 AEG-1 基因表达之间的相关性可能有助于识别相关生物标志物。本研究使用簇状规律间隔短回文重复序列（CRISPR）/Cas9 技术构建了三个 AEG-1 敲除 U251 细胞系，并评估了这些细胞系的生物学行为和代谢物比值。随着 AEG-1 表达的下降，AEG-1 敲除细胞系的凋亡率增加。同时，转移能力下降，总胆碱（tCho）和乳酸（Lac）的相对含量也降低。总之，AEG-1 表达的偏差影响 U251 细胞的凋亡率和转移能力，而 1H MRS 代谢物比值可以监测到这些变化。tCho/Cr 和 Lac/Cr 比值与 AEG-1 表达和恶性细胞行为呈正相关。本研究可能为神经胶质瘤的术前准确诊断和未来 AEG-1 靶向治疗评价提供潜在的生物标志物。
