GEO series

Targeting EZH2 and HDACs in hematological cancers induces transcriptional and metabolic deregulation causing ferroptosis

GSE306205 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2025/09/12 Platform GPL20301

At a glance

RNA-seq (gene expression) · human · 30 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 30 samples
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

The methyltransferase EZH2 functions as the enzymatic component of the PRC2 complex, which deposits methyl groups on H3K27, leading to chromatin condensation and gene repression. Recent studies have shown that EZH2 can also act as a transcriptional modulator, independently of the PRC2 complex and its methyltransferase activity. In this study, we demonstrate that EZH2 degradation is more effective in blocking cellular proliferation compared to EZH2 enzymatic inhibition.

Read the full summary ↓

Strikingly, the combination of EZH2 degradation and HDAC inhibition exhibited potent synergy in a broad spectrum of hematological malignancies. The dual inhibition led to increased H3K27 acetylation and transcriptional deregulation, revealing that the observed synergy is driven by metabolic reprogramming. A metabolism-centered analysis showed upregulation of cholesterol biosynthesis in several hematological malignancies upon combined inhibition of EZH2 and HDACs. Interestingly, EZH2 degradation and HDAC inhibition also independently modulate distinct metabolic pathways: EZH2 degradation enhances fatty acid biosynthesis, while HDAC inhibition activates the tricarboxylic acid (TCA) cycle. The overactivation of cholesterol and fatty acid synthesis, of the TCA cycle, and histone hyperacetylation, strongly suggests induction of metabolic stress. Indeed, as a result of EZH2 degradation and HDAC inhibition, we observed an increase of reactive oxygen species (ROS), promoting lipid peroxidation and ultimately triggering ferroptotic cell death. Together, our findings highlight that co-targeting EZH2 and HDAC leads to an increase of histone acetylation and the overactivation of several metabolic pathways, leading to strong metabolic stress and induction of ferroptotic cell death.

This dataset

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Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE306205_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1309678 and SRA study SRP610814. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

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+ 30 more — browse all 30 samples with per-sample file links →

Datasets on a similar topic

GSE254725 Dual targeting of EZH2 and Histone Deacetylases in hematological malignancies promotes transcriptional and metabolic deregulation leading to ferroptosis. 23 samples shares ezh2, hematological, deregulation, ferroptosis, targeting
GSE237951 Inhibition of EZH2 restores normal expression of genes associated with cysteine metabolism and ferroptosis in hepatocellular carcinoma [RNA-seq] 8 samples shares ezh2, ferroptosis
GSE176493 Comprehensive target engagement by EZH2 inhibitor CPI-0209 allows for preferential targeting of ARID1A mutant urothelial carcinoma 252 samples shares ezh2, targeting
GSE302321 Co-targeting EZH2 and TEAD elicits apoptosis through tumor-intrinsic innate immune signaling in Hippo pathway-mutated cancers - ChIP-seq data from genetic disruption of EZH2 41 samples shares ezh2, targeting
GSE300378 Targeting Thioredoxin Reductase 1 (TrxR1) Uncovers Ferroptosis-Linked Transcriptional Vulnerabilities in Lung Cancer 33 samples shares ferroptosis, targeting
GSE270021 Targeting ferroptosis resistance re-sensitizes metastatic HR+ HER2- breast cancer to palbociclib-hormone therapy 21 samples shares ferroptosis, targeting
GSE280581 Intragenic Epigenetic Deregulation by IDH2 Mutations Synergizes with SRSF2 Mutations Causing Mis-splicing of Key Transcriptional Regulators [RNA-seq] 20 samples shares deregulation, causing
GSE287645 Maternal cause of early-onset preeclampsia: excessive endometrial gland-derived apolipoprotein D induces placental ferroptosis and developmental abnormalities 16 samples shares ferroptosis, induces

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