Omics · study · 2026
P4HA3 drives cervical cancer lymphatic metastasis by facilitating ACLY-mediated ferroptosis resistance
Listed in NCBI GEO
The lymph node is the most common site of distant metastasis of cervical cancer (CCa), which elicits dismal prognosis and limited efficiency for treatment.
Description
Identification of the factors contributing to CCa lymphatic metastasis is needed to develop effective prevention and treatment strategies. Here, we found upregulation of prolyl 4-hydroxylase subunit alpha 3 (P4HA3), an α-subunit of prolyl hydroxylase, in lymphatic metastatic lesions of cervical cancer, which is strongly associated with poor prognosis.
In vitro and in vivo experiments showed that P4HA3 promoted CCa lymphatic metastasis by conferring ATP-citrate lyase (ACLY)-mediated ferroptosis resistance. Mechanistically, P4HA3 stabilizes ACLY protein by competitively inhibiting its interaction with the E3 ubiquitin ligase UBR4, which prevents UBR4-mediated proteasomal degradation of ACLY. ACLY-derived acetyl-CoA enhances H3K27 acetylation (H3K27Ac) modification level in the promoter of SLC7A11 gene, ultimately enhancing SLC7A11 transcription and ferroptosis resistance.
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Collectively, our study provides a mechanistic understanding of the interplay between ferroptosis resistance and lymph node metastasis, providing a possibility to combat lymph node metastasis in cervical cancer.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304077 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304077 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1298880 ncbi.nlm.nih.gov/bioproject/PRJNA1298880 ↗
project · from NCBI GEO
- PubMed 41381860 pubmed.ncbi.nlm.nih.gov/41381860 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE304077 | 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[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 |