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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1490878
This article is part of the Research Topic Post-Translational Modifications (PTMs) in Human Cancer: Pharmacological Insights and Therapeutic Opportunities View all 9 articles
Paromomycin targets HDAC1-mediated SUMOylation and IGF1R translocation in glioblastoma
Provisionally accepted- The First People's Hospital of Chenzhou, Chenzhou, China
Objective: This study investigates the effects of Paromomycin on SUMOylationrelated pathways in glioblastoma (GBM), specifically targeting HDAC1 inhibition. Methods: Using 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. Results: 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.
Keywords: Glioblastoma Multiforme, Paromomycin, HDAC1, Sumoylation, IGF1R, drug screening
Received: 03 Sep 2024; Accepted: 08 Nov 2024.
Copyright: © 2024 Guo, Min and Ning. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuejie Guo, The First People's Hospital of Chenzhou, Chenzhou, China
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