Towards Improved Brain Tumor Management: Novel Potential Therapeutic and Diagnostic Targets
Year: 2025
Type: conference-paper
Abstract: Introduction Glioblastomas are the most aggressive brain tumors (median survival 14.6 months) [1]. RNA methylation affects the cell cycle, structure, and stability of RNA molecules therefore plays a crucial role in cancer initiation and progression [2]. This modification is a promising avenue for gene therapy, targeting aberrant methylation patterns to personalize treatment. Transcription factor SOX2 is associated with glioma aggressiveness, poor prognosis, and growth [3]. Studying a modified form of SOX2 without C-terminal domain offers insights into its effects on glioma survival and proliferation. Combining SOX2 activity with RNA methylation uncovers new biomarkers and therapeutic targets for liquid biopsies, providing a less-invasive method to monitor glioma progression and treatment efficacy [4]. Demethylases ALKBH5 and FTO are linked to pro-oncogenic functions, promoting cell proliferation and selfrenewal, while BUD23 methyltransferase contributes to glioblastoma progression, suggesting their potential as biomarkers [5,6]. Aim This study aims to explore RNA methylation-associated biomarkers in gliomas to assess their diagnostic and therapeutic potential, enhancing personalized glioma management. Methods The research was conducted at the Lithuanian University of Health Sciences, Neuroscience Institute, Molecular Neurooncology Laboratory. In this study samples of cDNA from tumor biopsies of 54 patients with glioma were used, along with de-identified and encrypted clinical data. mRNA was extracted from U87 and U87 SOX2ΔC cell lines using TRIzol, followed by cDNA synthesis. Gene expression levels analyzed using RT-PCR and cell migration via wound-healing assay. Bioinformatic analysis was conducted using publicly available RNA sequencing data to evaluate the effects of ALKBH5 knockdown on gene expression and associated pathways using the open-access "Galaxy" platform. Statistical analyses were conducted using GraphPad Prism (p ≤ 0.05). Results ALKBH5, FTO, and BUD23 gene expression correlates with glioma malignancy, potentially serving as diagnostic markers. Higher gene expression linked to longer survival. Our study revealed associations between these genes and IDH mutation, gender, age, and survival. Additionally, we observed that SOX2ΔC influences ALKBH5 and BUD23 expression, suggesting its role in cancer development. ALKBH5 knockdown significantly altered gene expression and impacted key biological pathways, highlighting potential therapeutic benefits. Lastly, analysis identified novel glioma therapy targets based on their relevance to glioma function and use in other cancers. Conclusions Our findings demonstrate the potential of ALKBH5, FTO, and BUD23 as novel glioma biomarkers. Targeting these genes, along with exploring the role of SOX2 in regulating RNA methylation, may offer promising avenues for improved glioma treatment, possess prognostic and predictive value.
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7132228343
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