Min Zhong, Guo Yuejie, Ning Luo
The First People's Hospital of Chenzhou, Chenzhou, Hunan, China.
Front Pharmacol. 2024 Dec 11;15:1490878. doi: 10.3389/fphar.2024.1490878. eCollection 2024.
This study investigates the effects of Paromomycin on SUMOylation-related pathways in glioblastoma (GBM), specifically targeting HDAC1 inhibition.
Using TCGA and GTEx datasets, we identified SUMOylation-related genes associated with GBM prognosis. Molecular docking analysis suggested Paromomycin as a potential HDAC1 inhibitor. assays on U-251MG GBM cells were performed to assess Paromomycin's effects on cell viability, SUMOylation gene expression, and IGF1R translocation using CCK8 assays, qRT-PCR, and immunofluorescence.
Paromomycin treatment led to a dose-dependent reduction in GBM cell viability, colony formation, and migration. It modulated SUMO1 expression and decreased IGF1R nuclear translocation, an effect reversible by the HDAC1 inhibitor Trochostatin A (TSA), suggesting Paromomycin's involvement in SUMO1-regulated pathways.
This study highlights Paromomycin's potential as a therapeutic agent for GBM by targeting HDAC1-mediated SUMOylation pathways and influencing IGF1R translocation, warranting further investigation for its clinical application.
本研究调查了巴龙霉素对胶质母细胞瘤（GBM）中与类泛素化相关途径的影响，特别针对组蛋白去乙酰化酶1（HDAC1）抑制作用。
利用癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据集，我们鉴定了与GBM预后相关的类泛素化相关基因。分子对接分析表明巴龙霉素是一种潜在的HDAC1抑制剂。使用CCK8法、qRT-PCR和免疫荧光对U-251MG GBM细胞进行实验，以评估巴龙霉素对细胞活力、类泛素化基因表达和胰岛素样生长因子1受体（IGF1R）易位的影响。
巴龙霉素处理导致GBM细胞活力、集落形成和迁移呈剂量依赖性降低。它调节了类泛素化修饰蛋白1（SUMO1）的表达，并减少了IGF1R的核易位，组蛋白去乙酰化酶1抑制剂曲古抑菌素A（TSA）可逆转这一效应，表明巴龙霉素参与了SUMO1调节的途径。
本研究强调了巴龙霉素通过靶向HDAC1介导的类泛素化途径并影响IGF1R易位，作为GBM治疗药物的潜力，值得对其临床应用进行进一步研究。
