AUTHOR=Min Zhong , Guo Yuejie , Ning Luo 

TITLE=Paromomycin targets HDAC1-mediated SUMOylation and IGF1R translocation in glioblastoma

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1490878

DOI=10.3389/fphar.2024.1490878

ISSN=1663-9812

ABSTRACT=<sec><title>Objective</title><p>This study investigates the effects of Paromomycin on SUMOylation-related pathways in glioblastoma (GBM), specifically targeting HDAC1 inhibition.</p></sec><sec><title>Methods</title><p>Using TCGA and GTEx datasets, we identified SUMOylation-related genes associated with GBM prognosis. Molecular docking analysis suggested Paromomycin as a potential HDAC1 inhibitor. <italic>In vitro</italic> 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.</p></sec><sec><title>Results</title><p>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.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>