Omics · study · 2026
A telomerase-SUCLG2 signaling axis drives drug resistance by protecting persister cells [ATAC-Seq]
Listed in NCBI GEO
The evolution of drug-tolerant persister (DTP) cells into resistant clones remains a major obstacle to targeted therapies.
Description
Transcriptomic profiling across melanoma (A375, SK-MEL-28), non-small cell lung cancer (NSCLC; HCC827, PC-9), and colorectal cancer (CRC; SW480) models revealed a conserved biphasic telomerase regulation during DTP evolution. Combining targeted therapies with the telomere-dysfunction agent 6-thio-dG effectively suppressed DTP outgrowth and resistance in vitro and in vivo.
Mechanistically, 6-thio-dG induces chromatin remodeling, reducing SUCLG2 locus accessibility and downregulating this mitochondrial enzyme to disrupt DTP metabolic stability. Consistently, SUCLG2 knockdown recapitulated these therapeutic effects. Furthermore, in vivo RNAseq of HCC827 xenografts confirmed the combination coordinately suppresses mitochondrial metabolism, telomere maintenance, and persister programs.
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Collectively, preemptively combining 6-thio-dG with targeted therapies is a potent strategy to disrupt DTP evolution and overcome adaptive resistance across diverse malignancies.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE331nnn/GSE331127 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331127 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1466933 ncbi.nlm.nih.gov/bioproject/PRJNA1466933 ↗
project · from NCBI GEO
- PubMed 42418322 pubmed.ncbi.nlm.nih.gov/42418322 ↗
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 | GSE331127 | 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: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 |