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CX-5461 and Doxorubicin activate a shared DNA damage–associated transcriptional response in human cardiomyocytes

GSE302122 Homo sapiens (human) RNA-seq (gene expression) 144 samples Submitted 2025/12/11 Platform GPL34295
At a glance

RNA-seq (gene expression) · human · 144 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
144 samples: 48 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
CX-5461 and doxorubicin activate a shared DNA damage-associated transcriptional response in human cardiomyocytesG3 (Bethesda, Md.) · 2026
Summary (written by the submitters)
CX-5461 (CX) is under investigation for the treatment of late-stage cancers. While CX was first described as an RNA polymerase I inhibitor, it has recently been shown to primarily inhibit the beta isoform of topoisomerase II. This isoform is also inhibited by anthracycline drugs including Doxorubicin (DOX) and mediates the toxic effects of these drugs on the heart.
Read the full summary ↓
It is unclear whether CX will similarly cause cardiotoxicity. We therefore tested the effects of CX on iPSC-derived cardiomyocytes from six individuals. CX induces cell death in cardiomyocytes at micromolar concentrations. Transcriptome profiling following treatment over time reveals gene expression programs that correspond to the DNA damage response, which are pathways shared with DOX response genes. Micromolar CX concentrations affect heart-specific genes and 14 functionally-validated genes in loci associated with DOX cardiotoxicity. Our data demonstrate the impact of CX on the transcriptome of cardiomyocytes, a potential off-target cell type of the drug.
Published in
CX-5461 and doxorubicin activate a shared DNA damage-associated transcriptional response in human cardiomyocytes
Paul S, Gutiérrez JA, Bogar AR et al. · G3 (Bethesda, Md.) 2026 · PMID 41543508 · doi:10.1093/g3journal/jkag008
This dataset
Open GSE302122 in finder → Find more human RNA-seq datasets →
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 GSE302122_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 PRJNA1289016 and SRA study SRP599602. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41543508) ↗
Study design
48 conditions, mostly in triplicate
Ind1_CX_0.1 ×3 Ind1_CX_0.5 ×3 Ind1_DOX_0.1 ×3 Ind1_DOX_0.5 ×3 Ind1_VEH_0.1 ×3 Ind1_VEH_0.5 ×3 Ind2_CX_0.1 ×3 Ind2_CX_0.5 ×3 +40 more

Supports a between-group comparison across 144 samples.

How we read this: 48 replicated groups read from 144 sample titles; they account for 144 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

+ 104 more — browse all 144 samples with per-sample file links →

Datasets on a similar topic

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