Abstract:
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.
摘要:
高级别胶质瘤,包括多形性胶质母细胞瘤(GBM),仍然是成年人中主要的侵袭性脑肿瘤,以其快速增长和侵入性为标志。醛脱氢酶1家族,成员A1(ALDH1A1),一种酶,在肿瘤进展中起着重要作用,然而,其在高级别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GBM和LGG(低度胶质瘤)患者中ALDH1A1表达的预后意义。利用MTT和transwell检测U87细胞的生长和侵袭能力,分别。我们定量检查了细胞增殖(Ki-67和cyclinD1)和侵袭(MMP2和9)的标志物。进行Western印迹测试以确定ALDH1A1的下游信号传导。我们发现,与低级别胶质瘤相比,高级别胶质瘤中的ALDH1A1表达显着增加。过表达ALDH1A1的U87细胞显示增加的细胞生长和侵袭。我们发现ALDH1A1促进AKT的磷酸化,抑制AKT磷酸化减轻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GBM治疗的潜在治疗靶点.