A recent review published in the Genes & Diseases journal, by researchers from Medical University of Lodz, explores the role of SUMOylation, a post-translational modification, in the malignant transformation of glioblastoma, providing new insights into the identification of biomarkers and therapeutic targets.

The authors begin by outlining the SUMOylation process and its components. The E1-activating enzyme facilitates the activation of the SUMO protein, and Ubc9 (also known as UBE2I) catalyzes the transfer of the activated SUMO protein onto the target protein. Conversely, the SUMO proteases (SENPs) aid in deSUMOylation. The authors then list the SUMO target proteins, while describing how their SUMOylation influences the progression of various tumors.

Dysregulation of the SUMOylation mechanism is associated with cancer initiation and patient prognosis. Increasing evidence shows the critical role of SUMOylation in the development of gliomas. Enhanced SUMOylation increases the survival of GBM cells by protecting them from DNA damage, contributing to chemo- and radio-therapy resistance. SUMOylation affects cellular metabolism by enhancing the glycolytic and the pentose-phosphate pathways, thereby modifying the bioenergetics of the system. By stabilizing the Hif-1 alpha protein, it promotes the epithelial-to-mesenchymal transition of glioma cells.

The authors then describe the interplay between SUMOylation and phosphorylation processes during cell cycle regulation. SUMOylation stabilizes AKT activity, influencing proliferation, migration, and angiogenesis, while high AKT expression correlates with lower survival rates in GBM patients.

Furthermore, Ubc9 shows potential as a promising biomarker; its overexpression is associated with glioma progression, while its inhibition reduces proliferation and increases apoptosis of GBM cells. This suggests that Ubc9 and its associated molecular pathways may serve as potential therapeutic targets in glioma.
Numerous drugs and natural compounds, such as topotecan, chlorogenic acid, and melatonin, regulate SUMOylation to exert inhibitory effects on glioma progression.

The authors suggest that future research in glioma should be directed towards developing specific inhibitors, identifying predictive biomarkers, integrating SUMOylation-based therapies, and understanding its cross-talk with other PTMs and its role in glioma stem cells.
In conclusion, this review offers insights into the role of SUMOylation in GBM progression, suggesting that “targeting SUMOylation represents a promising but unexplored strategy in GBM treatment.”

Reference
Title of the original paper: Targeting SUMOylation in glioblastoma: A novel avenue for therapy and biomarker discovery

Journal: Genes & Diseases
Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

DOI: https://doi.org/10.1016/j.gendis.2025.101841

Funding Information:
Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Poland (No. 503/3-015-02/503-31-001)

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.

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