Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan.
Chem Biol Interact. 2024 Oct 1;402:111202. doi: 10.1016/j.cbi.2024.111202. Epub 2024 Aug 10.
High-grade gliomas, including glioblastoma multiforme (GBM), continue to be a leading aggressive brain tumor in adults, marked by its rapid growth and invasive nature. Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), an enzyme, plays a significant role in tumor progression, yet its function in high-grade gliomas is still poorly investigated. In this study, we evaluated ALDH1A1 levels in clinical samples of GBM. We also assessed the prognostic significance of ALDH1A1 expression in GBM and LGG (low grade glioma) patients using TCGA (The Cancer Genome Atlas) database analysis. The MTT and transwell assays were utilized to examine cell growth and the invasive capability of U87 cells, respectively. We quantitatively examined markers for cell proliferation (Ki-67 and cyclin D1) and invasion (MMP2 and 9). A Western blot test was conducted to determine the downstream signaling of ALDH1A1. We found a notable increase in ALDH1A1 expression in high-grade gliomas compared to their low-grade counterparts. U87 cells that overexpressed ALDH1A1 showed increased cell growth and invasion. We found that ALDH1A1 promotes the phosphorylation of AKT, and inhibiting AKT phosphorylation mitigates the ALDH1A1's effects on tumor growth and migration. In summary, our findings suggest ALDH1A1 as a potential therapeutic target for GBM treatment.
高级别神经胶质瘤,包括多形性胶质母细胞瘤(GBM),仍然是成人中一种具有侵袭性的主要脑肿瘤,其特点是生长迅速且具有侵袭性。醛脱氢酶 1 家族成员 A1(ALDH1A1)是一种酶,在肿瘤进展中起着重要作用,但它在高级别神经胶质瘤中的功能仍未得到充分研究。在这项研究中,我们评估了 GBM 临床样本中的 ALDH1A1 水平。我们还使用 TCGA(癌症基因组图谱)数据库分析评估了 ALDH1A1 表达在 GBM 和 LGG(低级别神经胶质瘤)患者中的预后意义。MTT 和 Transwell 测定分别用于检测 U87 细胞的生长和侵袭能力。我们定量检测了细胞增殖(Ki-67 和细胞周期蛋白 D1)和侵袭(MMP2 和 9)的标志物。Western blot 检测用于确定 ALDH1A1 的下游信号。我们发现高级别神经胶质瘤中 ALDH1A1 的表达明显增加,而低级别神经胶质瘤则相对较低。过表达 ALDH1A1 的 U87 细胞表现出增强的细胞生长和侵袭能力。我们发现 ALDH1A1 促进 AKT 的磷酸化,抑制 AKT 磷酸化可减轻 ALDH1A1 对肿瘤生长和迁移的影响。总之,我们的研究结果表明 ALDH1A1 是治疗 GBM 的潜在治疗靶点。