Language

English

Publication Date

3-1-2025

Journal

Molecular Oncology

DOI

10.1002/1878-0261.13735

PMID

39323013

PMCID

PMC11887672

PubMedCentral® Posted Date

9-25-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Glioblastoma is the most common primary malignant brain tumor in adults, with a median survival of just over 1 year. The failure of available treatments to achieve remission in patients with glioblastoma (GBM) has been attributed to the presence of cancer stem cells (CSCs), which are thought to play a central role in tumor development and progression and serve as a treatment-resistant cell repository capable of driving tumor recurrence. In fact, the property of "stemness" itself may be responsible for treatment resistance. In this study, we identify a novel long noncoding RNA (lncRNA), cancer stem cell-associated distal enhancer of SOX2 (CASCADES), that functions as an epigenetic regulator in glioma CSCs (GSCs). CASCADES is expressed in isocitrate dehydrogenase (IDH)-wild-type GBM and is significantly enriched in GSCs. Knockdown of CASCADES in GSCs results in differentiation towards a neuronal lineage in a cell- and cancer-specific manner. Bioinformatics analysis reveals that CASCADES functions as a super-enhancer-associated lncRNA epigenetic regulator of SOX2. Our findings identify CASCADES as a critical regulator of stemness in GSCs that represents a novel epigenetic and therapeutic target for disrupting the CSC compartment in glioblastoma.

Keywords

Glioblastoma, RNA, Long Noncoding, Humans, Neoplastic Stem Cells, SOXB1 Transcription Factors, Cell Differentiation, Brain Neoplasms, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Enhancer Elements, Genetic, Epigenesis, Genetic, cancer stem cells, cell differentiation, enhancers, long noncoding RNA, SOX2, super‐enhancers

Published Open-Access

yes

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