Omics · study · 2026
Effect of HDAC3 knockdown on H3K9ac in osteosarcoma cells
Listed in NCBI GEO
The dearth of molecular and cellular knowledge regarding the etiology of osteosarcoma (OS) impedes the advancement of innovative therapeutic interventions, such as immune therapy, for this debilitating childhood malignancy.
Description
Here, we report that Runt-related transcription factor 2 (RUNX2), along with nuclear receptor corepressor (NCOR1), inhibits OS cell senescence by downregulating the cGAS-STING-Type I Interferon (IFN-I) axis.
We demonstrate that the NCOR1 gene is amplified in human OS tumors and is essential for tumor growth in xenograft mouse models. RUNX2 and NCOR1 function as regulatory “rheostats” by directly suppressing the expression of key transducer genes within the cGAS-STING-IFN-I pathway, including cGAS, STING, STAT1, STAT2, IRF7, and IRF9. During OS senescence induced by depletion of RUNX2 or NCOR1, endogenous retroviruses are aberrantly upregulated and reverse-transcribed, activating cGAS and initiating an elevated inflammatory cascade that includes programmed death-ligand 1 (PD-L1) upregulation.
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Inhibition of histone deacetylase 3 (HDAC3), a component of the NCOR1 complex, mirrors the effects observed with RUNX2 or NCOR1 depletion. Moreover, combining an HDAC3 inhibitor (HDAC3i) with an anti-PD-1 antibody results in sustained OS regression and increased CD8+ T cell activation in a mouse model. In conclusion, our findings identify RUNX2-NCOR1 as an epigenetic checkpoint modulating the innate immunity of OS cells, providing a rationale for the combined use of HDAC3i-targeted therapy and immune checkpoint blockade in OS treatment.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE344nnn/GSE344566 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE344566 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1516091 ncbi.nlm.nih.gov/bioproject/PRJNA1516091 ↗
project · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE344566 | 14 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 (65%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-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 |