Omics · study · 2026
A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer.
Listed in NCBI GEO
Although most prostate tumors are relatively indolent, advanced disease can progress to aggressive, often lethal variants, including neuroendocrine prostate cancer (NEPC).
Description
To identify drivers of aggressive prostate cancer, we used Sleeping Beauty (SB) transposon mutagenesis in a mouse model having prostate-specific loss of Pten and Tp53 (NPp53 mice). Compared with control NPp53-SB(—) mice, experimental NPp53-SB(+) mice developed more aggressive tumors with increased metastasis.
Notably, NPp53-SB(+) mice exhibited NEPC phenotypes with transcriptomic features that recapitulate human NEPC. Analysis of recurrent common insertion sites (CIS) and associated genes (CIS-genes) identified genes differentially expressed between NEPC and non-NEPC tumors. Analysis of NEPC-enriched CIS genes by cross-species integration of genomic and transcriptomic data prioritized Sirtuin 1 (Sirt1) as a candidate mechanistic determinant of NEPC.
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Gain- and loss-of-function studies in human prostate cancer cells and mouse NEPC organoids confirmed that SIRT1 promotes NEPC, while pharmacological inhibition suppresses it. Thus, integration of cross-species analyses with an unbiased forward genetic screen uncovered novel drivers of NEPC.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE271nnn/GSE271066 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE271066 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1129532 ncbi.nlm.nih.gov/bioproject/PRJNA1129532 ↗
project · from NCBI GEO
- PubMed 39253480 pubmed.ncbi.nlm.nih.gov/39253480 ↗
publication · from NCBI GEO
- PubMed 42207152 pubmed.ncbi.nlm.nih.gov/42207152 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus · Other
- From keywords
- Life Sciences
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE271066 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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[method].geo_series_type:other | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | 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 |