Epitranscriptomic studies of glioblastoma: Analysis of gene expression in tumour cells and tumour tissues

Background. Glioblastomas are the most aggressive and lethal primary brain tumours, with a median survival of 14.6 months [1]. RNA methylation is a post-transcriptional modification that regulates RNA translation, splicing, and stability, which may contribute to cancer initiation and progression [2]. With the rise of personalised medicine need, it is believed that aberrant RNA methylation patterns present a novel opportunity for targeted gene therapy and early diagnostics. The expression of the transcription factor SOX2 is associated with a poor prognosis and is essential for glioma stemness and malignancy [3]. Investigating a modified SOX2 variant lacking the C-terminal domain, which is crucial for transcriptional activation, reveals its regulatory impact on glioma cell survival and proliferation. Integrating SOX2 activity with RNA methylation may uncover potential biomarkers that could facilitate liquid biopsy development, providing a minimally invasive approach to diagnose and treat gliomas, monitor progression and effectiveness of the treatment [4]. Aim. This study aims to identify novel biomarkers for early glioma diagnostic and targeted gene therapy. Methods. Samples of copy DNA from tumour biopsies of 54 glioma patients were analysed with de-identified clinical data. mRNA extracted from U87 and U87 SOX2ÄC cell lines was used for cDNA synthesis. Gene expression (RT-PCR) and cell migration (wound-healing assay) were assessed. Bioinformatic analysis of publicly available RNA sequencing data explored the impact of ALKBH5 knockdown on gene expression and related pathways. Statistical significance was determined at p 0.05. Results. This study found that ALKBH5, FTO, and BUD23 expression levels correlated with glioma malignancy and patient survival, suggesting their potential as diagnostic biomarkers. Higher gene expression linked to longer survival. Significant associations were observed between these genes and clinical factors, including IDH mutation status, age, and gender. Furthermore, we demonstrate that SOX2ÄC influences ALKBH5 and BUD23 expression, indicating its involvement in glioma development. Knockdown of ALKBH5 significantly altered gene expression profiles and impacted crucial biological pathways, suggesting potential therapeutic benefits. Additionally, novel glioma therapy targets were identified based on their functional relevance and prior use in other cancers. Conclusion. This study suggests that ALKBH5, FTO, and BUD23 may serve as novel glioma biomarkers with prognostic value. Further research into targeting these genes and investigation of SOX2’s role in RNA methylation may improve glioma treatment strategies.