Omics · study · 2026
KAT2B-Mediated Epigenetic Suppression of RAD51C Enhances Olaparib Sensitivity in Colorectal Cancer
Listed in NCBI GEO
By blocking poly ADP ribose polymerase (PARP), olaparib prevents DNA damage repair, particularly in tumors that have a BRCA1/2 mutation or are BRCA-positive.
Description
Nevertheless, a Phase II study of 33 CRC patients receiving mono-Olaparib therapy revealed that some of these individuals still had resistance to Olaparib while having poor DNA damage repair. RAD51 reversion mutations are a frequent cause of resistance to PARP inhibitors in cancers that do not have BRCA mutations.
Though little is known, a number of tactics have been studied when combining PARPi with other inhibitors. Here, we introduce the enzyme KAT2B as a protein involved in transcription that is connected to RAD51C, reducing the levels of RAD51C by lowering the acetylation of Histone H3 (H3K27) at the beginning of the RAD51C gene. Consequently, colorectal cancer cells become more vulnerable to Olaparib therapy.
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The H3K27ac binding domain is necessary for the transcription of RAD51C. We find that a subpopulation of tumor cells expressing RAD51C have reduced endogenous KAT2B expression. This expression leads to increased DNA damage accumulation and decreased PARPi resistance in RAD51C-expressing cells.
According to our findings, RAD51C-expressing cells' RAD51C and PARPi responses are significantly regulated by KAT2B and histone acetylation. This information offers vital new understandings into the molecular requirements for focusing on BRCA-functional malignancies.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE267nnn/GSE267911 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE267911 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1113624 ncbi.nlm.nih.gov/bioproject/PRJNA1113624 ↗
project · from NCBI GEO
- PubMed 41826541 pubmed.ncbi.nlm.nih.gov/41826541 ↗
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 | GSE267911 | 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 |