Epigenetic Regulation of OLIG2 in Glioblastoma: Mechanisms and Therapeutic Targets to Combat Treatment Resistance.
Publication Title
Journal of molecular neuroscience : MN
Document Type
Article
Publication Date
8-31-2025
Keywords
Glioblastoma; Humans; Oligodendrocyte Transcription Factor 2; Epigenesis, Genetic; Brain Neoplasms; MicroRNAs; Drug Resistance, Neoplasm; Animals; Gene Expression Regulation, Neoplastic; Cancer; Glioblastoma; Glioma; Olig2; Transcription factor, Single-cell RNA sequencing, Kaplan–Meier survival curves.
Abstract
Glioblastoma (GBM) represents one of the most aggressive brain tumors with a poor prognosis despite decades of research. Epigenetic regulation has emerged as a promising strategy for managing aggressive cancers, such as GBM, by modulating pro-tumorigenic gene expression. The role of pro-tumorigenic genes, such as oligodendrocyte transcription factor 2 (OLIG2), has been heavily associated with cancer progression and treatment resistance and is a potential target for GBM. The objective of this study is to analyze the effectiveness of various epigenetic regulators, including histone modifiers, DNA methylases, chromatin remodelers, and miRNAs, on OLIG2 expression, including the effectiveness of individual epigenetic regulators and their combinations. The effects of epigenetic regulators in GBM that are found in the literature were reviewed for their survival and co-expression with OLIG2. We found that KDM6B, BRG1, DNMT1, and HDAC2 were associated with significant co-expression with OLIG2 and decreased survival in GBM patients, reinforcing their suitability as targets. Additionally, miR-17-3p miRNAs associated with silencing OLIG2 as gene expression was downregulated in GBM. Additionally, this paper highlights the potential of combination therapies targeting multiple epigenetic pathways simultaneously. A kinase inhibitor (alisertib), together with JQ1, reduced the tumor growth of GBM cells in vivo more than either treatment alone, making combination therapies a promising solution.
Area of Special Interest
Neurosciences (Brain & Spine)
Area of Special Interest
Cancer
Specialty/Research Institute
Neurosciences
Specialty/Research Institute
Oncology
DOI
10.1007/s12031-025-02402-y
