Excel · study · 2026
WTAP stability enhanced by USP7 promotes enzalutamide resistance in prostate cancer via activating AKT signaling
Listed in NCBI GEO
Castration-resistant prostate cancer (CRPC) is one of the most prevalent cancers in men.
Description
The new generation androgen receptor (AR) inhibitor enzalutamide can improve therapeutic effectiveness of patients with CRPC. However, these patients eventually develop to acquired enzalutamide resistance (ENZR), and the mechanisms underlying resistance is not well understood.
Wilms’ tumor 1-associating protein (WTAP) plays an important role in m6A modification and has been reported as an oncogene in various cancers. Here, we utilized a tissue microarray and collected tissues from prostate cancer (PCa) patients to detect WTAP expression, and found that WTAP is upregulated in PCa. Meanwhile, WTAP over-expression promotes cell proliferation and accelerates tumor growth through colony formation assays and establishing subcutaneous xenograft model in vivo.
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These findings establish the tumor promoter role of WTAP in prostatic tumorigenesis. Furthermore, we verified that WTAP is a novel responsive gene of AR via promoter activity and chromatin immunoprecipitation (ChIP) assays. Importantly, we uncovered WTAP is upregulated in ENZR cells and WTAP knockdown inhibited the proliferation of ENZR cells.
Mechanistically, ubiquitin-specific protease (USP7) enhanced the stability of WTAP by ubiquitin-proteasome pathway in ENZR cells, thereby WTAP increase promotes AKT signaling through m6A mediated way and AKT inhibitor can abolished the pro-resistance phenotype mediated by WTAP. Together, these findings suggest that WTAP plays a key role in ENZR development of PCa cells and WTAP may be a potential treatment target for ENZR tumors.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301437 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301437 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1285172 ncbi.nlm.nih.gov/bioproject/PRJNA1285172 ↗
project · from NCBI GEO
- PubMed 41981278 pubmed.ncbi.nlm.nih.gov/41981278 ↗
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 | GSE301437 | 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 |