Paromomycin targets HDAC1-mediated SUMOylation and IGF1R translocation in glioblastoma

ObjectiveThis study investigates the effects of Paromomycin on SUMOylation-related pathways in glioblastoma (GBM), specifically targeting HDAC1 inhibition.MethodsUsing TCGA and GTEx datasets, we identified SUMOylation-related genes associated with GBM prognosis. Molecular docking analysis suggested...

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Bibliographic Details
Main Authors: Zhong Min, Yuejie Guo, Luo Ning
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1490878/full
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Summary:ObjectiveThis study investigates the effects of Paromomycin on SUMOylation-related pathways in glioblastoma (GBM), specifically targeting HDAC1 inhibition.MethodsUsing TCGA and GTEx datasets, we identified SUMOylation-related genes associated with GBM prognosis. Molecular docking analysis suggested Paromomycin as a potential HDAC1 inhibitor. In vitro 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.ResultsParomomycin 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.ConclusionThis 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.
ISSN:1663-9812