The Epigenetic Inhibition of EZH2 in Glioblastoma Multiforme: Identifying Potential Therapeutic Targets

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2023-09-18

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Saudi Digital Library

Abstract

Glioblastoma multiforme (GBM), a highly aggressive primary brain tumor, presents significant challenges in terms of prognosis and treatment response. This study delves into the molecular intricacies of GBM, highlighting its intratumoral heterogeneity and classification into distinct subtypes with diagnostic and prognostic implications. Additionally, the role of glioma stem cells (GSCs) in GBM aggressiveness and resistance to therapy is examined, shedding light on potential therapeutic avenues. Our primary objective is to assess the effects of EZH2 inhibition, achieved through EZP and GSK inhibitors, on gene expression profiles in G7 cell lines derived from GBM. This investigation employs RNA-seq analysis to elucidate differential gene expression patterns post-EZH2 inhibition. Furthermore, we utilize ChIP-seq analysis to pinpoint direct therapeutic targets influenced by EZH2, with a focus on transcription start sites (TSS) in promoter regions. Our findings reveal a cohort of genes highly expressed in GSCs under EZH2 inhibition, including COL4A1, COL4A2, COL4A3, COL4A4, COL6A2, SYT3, BMI-1, BMP9, CHRD, NGFR, CD44, CD24, SYP, ATP1A3, ATPB2, CPE, and BCL. These discoveries provide valuable insights into the potential of EZH2 inhibition in attenuating GSCs and present promising opportunities for the development of novel therapeutic strategies in the treatment of glioblastoma.

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RNA-seq analysis, Glioblastoma multiform, Chip-seq analysis, EZH2, H3k27me3, brain tumor

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