The role of ALDH1A1 in glioblastoma proliferation and invasion

IF 4.7 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Chemico-Biological Interactions Pub Date : 2024-08-10 DOI:10.1016/j.cbi.2024.111202
Yu-Kai Huang , Tzu-Ming Wang , Chi-Yu Chen , Chia-Yang Li , Shu-Chi Wang , Khushboo Irshad , Yuan Pan , Kun-Che Chang
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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.

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ALDH1A1 在胶质母细胞瘤增殖和侵袭中的作用
包括多形性胶质母细胞瘤(GBM)在内的高级别胶质瘤仍是成人中主要的侵袭性脑肿瘤,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)是一种在肿瘤进展过程中起重要作用的酶,但其在高级别胶质瘤中的功能仍未得到充分研究。本研究评估了 GBM 临床样本中的 ALDH1A1 水平。我们还利用 TCGA(癌症基因组图谱)数据库分析评估了 ALDH1A1 表达在 GBM 和 LGG(低级别胶质瘤)患者中的预后意义。我们利用 MTT 和 transwell 试验分别检测了 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)的标记物。我们还进行了一项 Western 印迹测试,以确定 ALDH1A1 的下游信号转导。我们发现,与低级别胶质瘤相比,高级别胶质瘤中 ALDH1A1 的表达明显增加。过表达 ALDH1A1 的 U87 细胞显示出细胞生长和侵袭的增加。我们发现,ALDH1A1 可促进 AKT 的磷酸化,而抑制 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。
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来源期刊
CiteScore
7.70
自引率
3.90%
发文量
410
审稿时长
36 days
期刊介绍: Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes. Special emphasis is placed on toxicological mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro. Endpoints of interest include, but are not limited to carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.
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