Omics · study · 2026
Anti-cervical cancer activity of SRI-42127 via inducing DNA damage and activating p53, while reducing HuB, HuR, and HPV E6 E7 proteins
Listed in NCBI GEO
High-risk human papillomaviruses (HR-HPVs) drive 95% of cervical cancers (CaCx) and a significant fraction of other ano-genital and oropharyngeal cancers.
Description
Analyses of transcriptomes of normal and HPV-infected tissues have previously identified 95 differentially expressed RNA binding proteins known to associate with cancer-related pathways. One of them ELAVL2/HuB is a member of the ELAVL family, which includes the ubiquitous, well-studied ELAVL1/HuR.
Elevated levels of HuR and HuB proteins have been reported in HPV cancers. However, information regarding their roles in HPV pathobiology is limited. SRI-42127, an inhibitor of HuR dimerization, essential for its activity, has shown promise in reducing the growth of glioblastoma xenografts.
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In this study, we explored the therapeutic potential of SRI-42127 to treat HPV-associated CaCx. Our findings demonstrate that HR-HPV E6 and E7 oncogenes regulate the abundance and subcellular localization of HuB and HuR proteins and that HuB interacts with HuR. SRI-42127 reduces HuR and HuB proteins and induces cell cycle arrest and apoptosis in CaCx cell lines.
Unexpectedly, these effects are attributable to a previously unknown ability of SRI-42127 to induce DNA damage, which decreases HPV E6 and E7 proteins and stabilizes transcriptionally active p53. Mechanistically, HuB-knockdown induces DNA-damage and stabilizes p53. SRI-42127 curtails tumor growth of mouse HPV-16+ TC-1 transformed cells in syngeneic mice.
Additionally, SRI-42127 complements cisplatin in inhibiting the growth of a CaCx cell line in 3D cultures and HPV-16+ CaCx PDX. Collectively, these findings suggest that SRI-42127 restores p53 functions in HPV+ CaCx and enhances sensitivity to conventional chemotherapies, potentially benefiting CaCx patients.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE255nnn/GSE255374 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE255374 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1074762 ncbi.nlm.nih.gov/bioproject/PRJNA1074762 ↗
project · from NCBI GEO
- PubMed 42647117 pubmed.ncbi.nlm.nih.gov/42647117 ↗
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%
Related
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE255374 | 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 |