This work explores how Paromomycin influences SUMOylation-associated signaling in glioblastoma (GBM), with a particular focus on its inhibitory action on HDAC1. SUMOylation-related genes linked to GBM outcomes were screened using TCGA and GTEx datasets. Molecular docking predicted Paromomycin as a likely HDAC1 inhibitor. Functional experiments in U-251MG GBM cells—including CCK8 viability assays, qRT-PCR, and immunofluorescence—were conducted to evaluate its impact on SUMOylation gene activity, cell growth, and IGF1R trafficking. Paromomycin reduced GBM cell survival, colony formation, and migratory capacity in a concentration-dependent manner. It altered SUMO1 expression and suppressed IGF1R entry into the nucleus, an effect counteracted by the HDAC1 inhibitor Trichostatin A (TSA), supporting a role for Paromomycin in SUMO1-dependent regulatory mechanisms. These findings position Paromomycin as a promising GBM therapeutic candidate through its modulation of HDAC1-driven SUMOylation processes and regulation of IGF1R nuclear transport, emphasizing the need for further clinical-oriented studies.
