Omics · study · 2026
PCSK9 promotes prostate cancer via facilitating intratumoral cholesterol accumulation and enhancing immunosuppressive tumor microenvironment
Listed in NCBI GEO
Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes prostate cancer (PC) progression through enhancement of intratumoral cholesterol accumulation and modulation of the tumor immune microenvironment.
Description
To investigate the transcriptomic effects of PCSK9 in vivo, we performed RNA sequencing of LNCaP xenograft tumors grown under intact (non-castrated) conditions, comparing tumors overexpressing PCSK9-WT, PCSK9-D374Y, PCSK9-Q152H, or an empty vector (EV).
These transcriptomic data reveal that PCSK9 overexpression is associated with increased expression of angiogenesis-related genes, nuclear receptor signaling components, and immunomodulatory pathways. While functional in vivo studies further show that PCSK9 promotes LNCaP tumor growth under both intact and castrated conditions, the RNA-seq dataset presented here specifically captures the transcriptional landscape of tumors under intact conditions only.
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Beyond the xenograft model, we demonstrate that PCSK9 is upregulated in primary, metastatic, and castration-resistant PC (CRPC), as well as in the Pten-null mouse model of PC. In TRAMP mice, PCSK9 inhibition or deletion reduces intratumoral cholesterol, suppresses tumor progression, delays CRPC onset, and increases CD8+ T cell infiltration. Transcriptomic profiling identifies a 15-gene immune-related signature (Sig15IM) regulated by PCSK9, with ABI3 and CORO1A showing strong co-expression with immune checkpoints across multiple prostate and pan-cancer datasets.
These findings provide insight into how PCSK9-driven transcriptional programs contribute to cholesterol metabolism and immune suppression in prostate cancer, and highlight PCSK9 as a therapeutic co-target to mitigate androgen deprivation therapy (ADT) resistance.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE294nnn/GSE294071 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294071 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1247991 ncbi.nlm.nih.gov/bioproject/PRJNA1247991 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE294071 | 12 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[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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |