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Epigenetic library screen reveals novel targets for uveal melanoma

GSE294950 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2025/04/22 Platform GPL29480
At a glance

RNA-seq (gene expression) · human · 24 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)
Topic
Uveal melanomaThis series is part of our curated briefing on it.
Samples
24 samples: 8 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
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.
Paper
Identification of targetable epigenetic vulnerabilities for uveal melanomaCell death & disease · 2025
Summary (written by the submitters)
Uveal melanoma (UM) is the most common primary ocular cancer in adults, which metastasizes mainly to the liver in around half of the cases. The limited potency of current treatment options for metastatic UM necessitates an urgent exploration of novel therapeutic approaches to improve patient prognosis. We conducted a large epigenetic compound library screen with the currently most well characterized, focused epigenetics library available, which consists of 932 potent, cell permeable, medically active, epigenetic-directed small molecule modulators.
Read the full summary ↓
Our screening identified two new lead compounds, which so-far have been unappreciated for UM. Romidepsin, an HDAC inhibitor with specificity for class I HDACs, was the most efficient compound in-vitro, as well as the BET inhibitor Mivebresib, which showed minimal toxicity on normal cells. RNA sequencing and pathway analysis revealed an upregulation of PRC-associated gene targets induced by HDAC inhibition, while BET inhibition appears to act through retinoic acid related pathways. Mivebresib treatment in a metastatic uveal melanoma mouse model resulted in longer survival times and reduced metastasis to the spinal cord and brain. The results of our drug screen indicate a vulnerability for HDAC and BET inhibition for UM cells. The BET inhibitor Mivebresib may be a promising candidate for future synergistic and clinical trials.
Published in
Identification of targetable epigenetic vulnerabilities for uveal melanoma
Yenisehirli G, Borges S, Braun SS et al. · Cell death & disease 2025 · PMID 41387414 · doi:10.1038/s41419-025-08295-4
This dataset
Open GSE294950 in finder → Find more human RNA-seq datasets → Uveal melanoma landscape →
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 GSE294950_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 PRJNA1252089 and SRA study SRP579444. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41387414) ↗
Study design
8 conditions, mostly in triplicate
MP41 cells, 24 hour 0.1% DMSO treatment, samp… ×3 MP41 cells, 24 hour Quisinostat treatment, sa… ×3 MP41 cells, 24 hour Mivebresib treatment, sam… ×3 MP41 cells, 24 hour Romidepsin treatment, sam… ×3 MP46 cells, 24 hour 0.1% DMSO treatment, samp… ×3 MP46 cells, 24 hour Quisinostat treatment, sa… ×3 MP46 cells, 24 hour Mivebresib treatment, sam… ×3 MP46 cells, 24 hour Romidepsin treatment, sam… ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 replicated groups read from 24 sample titles; they account for 24 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
More Uveal melanoma datasets

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.