Omics · study · 2026
Targeting HDAC and proteostasis to eradicate quiescent cancer cells
Listed in NCBI GEO
Chemotherapy remains the primary treatment for ovarian cancer (OvCa), and chemoresistance drives patient mortality.
Description
Cellular quiescence, reversible exit from the cell cycle, increases chemotherapy resistance as chemotherapies primarily target rapidly proliferating cells. Here, we report that CHD4 and MBD3, components of the nucleosome remodeling and deacetylase (NuRD) complex, are downregulated in quiescent OvCa cells (qOvCa).
We find that either CHD4 or MBD3 knockdown or histone deacetylase inhibitors (HDACi), induce quiescence in OvCa cells. RNA-Seq and ATAC-seq analysis of HDACi-treated cells confirmed expression changes consistent with induction of quiescence. Additionally, HDACi treated cells revealed downregulation of the RHO/RAC pathways.
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Suggesting downregulation of the RAC pathway could play a role in HDACi-mediated quiescence, RAC inhibitors (RACi) similarly induced quiescence. Both HDACi and RACi resulted in nuclear-to-cytoplasmic shifting of the pro-proliferative transcription factor MRTFA. which has been linked to quiescence. Further analysis of HDACi qOvCa indicated multiple alterations in proteostasis, including increased proteasome activity and autophagy.
We find qOvCa cells are dependent on these pathways for survival, such that there is profound synergistic OvCa cell death with HDACi and proteasome- or autophagy-inhibitor combination therapy. Combined, this work supports HDACi as pharmacologic means to induce a quiescent state in OvCa cells and sensitize them to proteostasis-targeting drugs.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317616 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317616 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1414556 ncbi.nlm.nih.gov/bioproject/PRJNA1414556 ↗
project · from NCBI GEO
- PubMed 42595792 pubmed.ncbi.nlm.nih.gov/42595792 ↗
publication · 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 75% · RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE317616 | 11 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:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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 |