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An EGFR Co-amplified Long Noncoding RNA HELDR Promotes Glioblastoma Malignancy through KAT7-driven gene programs [KAT7]

GSE286319 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2026/02/07 Platform GPL34281
Summary
EGFR amplification at extrachromosome DNAs (ecDNAs) is a major driving mutation in glioblastoma (GBM). However, targeting EGFR for GBM treatments remain unsatisfied. Here we identify a de novo long non-coding RNA (lncRNA) that is co-amplified with EGFR which we named hidden EGFR long non-coding downstream RNA (HELDR). HELDR is a GBM-specific lncRNA that promotes tumorigenicity independent of EGFR expression and signaling. HELDR globally binds genomic DNA and recruits a transcription co-activator p300 to the promoter of KAT7. p300-induced H3K27ac at KAT7 promoter enlists other co-transcription factors, activating KAT7 transcription. KAT7 induces H3K14ac H4K12ac that activate the transcription of KAT7-targeting gene programs critical for GBM malignancy. Targeting KAT7 synergistically enhances therapeutic effects of targeting EGFR for GBM treatment. These results not only reveal the role of HELDR in EGFR-driven GBM malignancy, but also provide strong rationale to characterize the roles of lncRNAs co-amplified with driver oncogenes at ecDNAs in human cancers.
Published in
An EGFR co-amplified lncRNA HELDR promotes glioblastoma malignancy through KAT7-driven gene programs
Yu X, Song X, Schäfer RA et al. · Nature cell biology 2026 · PMID 41896311 · doi:10.1038/s41556-026-01924-w
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Also filed as BioProject PRJNA1208669 and SRA study SRP556388. Searching any of these in the dataset finder brings you back here.

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