Omics · study · 2026
Progressive suppression of DNA repair genes with persistent p53 activation in Doxorubicin-treated cardiomyocytes
Listed in NCBI GEO
Doxorubicin (DOX) is an effective anti-cancer drug; however it can cause cardiotoxicity by inducing DNA double strand breaks in cardiomyocytes.
Description
Cardiotoxicity can present immediately or years following treatment. Most human in vitro models of DOX-induced cardiotoxicity (DIC) focus on the acute effects of DOX treatment.
To understand the long-term effects, we profiled the global gene expression response to DOX exposure over time. We treated iPSC-derived cardiomyocytes from six individuals with DOX for 24 hours and assayed responses after 0, 24 and 144 hours of recovery. DNA damage, determined by γH2AX expression, is induced following DOX treatment and is resolved by the last recovery timepoint.
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We identified both acute and chronic gene expression response signatures. The chronic signature, representing 501 genes, is enriched for p53 target genes and DNA damage response genes compared to acute response genes. P53 target genes are persistently activated, and DNA damage response genes are progressively downregulated over time.
Our results suggest an altered cell state following repair of double strand breaks that is distinct from pre-exposed cells. DOX response genes with persistent changes in expression can be applied to the design of toxicity biomarkers or therapeutic targets.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313746 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313746 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1381534 ncbi.nlm.nih.gov/bioproject/PRJNA1381534 ↗
project · from NCBI GEO
- PubMed 42324868 pubmed.ncbi.nlm.nih.gov/42324868 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE313746 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |