Omics · study · 2026
AP-1 Mediates Oncogenic Transcription and Predicts Fatality in Lung Squamous Cell Carcinoma Patients [ChIP-seq]
Listed in NCBI GEO
Despite the growing volume of genomic data, there remains a gap in our understanding of the mechanisms driving oncogenic transcription during non-small cell lung cancer (NSCLC) progression.
Description
In this study, we employed a model cell line-guided, multi-omic approach including promoter-capture Hi-C, ATAC-Seq, transcriptomics, and epigenomics, to uncover the epigenomic and three-dimensional (3D) genomic alterations on oncogenes in NSCLC patients from the Cancer Genome Atlas (TCGA).
Our model cell lines recapitulate key aspects of the transcriptomic and chromatin-accessibility changes observed in NSCLC patients. ChIP-Seq analysis in model cell lines, revealed increased activity at promoters and enhancers, but decreased activity at insulators in NSCLC patients. We identified several increased promoter-enhancer interaction events in upregulated oncogenes.
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These aberrant enhancer-promoter looping events were mediated by the transcription factor AP-1. Survival analysis revealed a significant correlation between AP-1 expression levels and mortality in lung squamous carcinoma patients, but not in lung adenocarcinoma patients. Inhibition of AP-1, using AP-1 or JNK inhibitors, suggests that the abnormal activity of AP-1 is modulated by JNK kinases within the MAPK pathway, which promotes oncogenic transcription in NSCLC.
These findings highlight the role of AP-1 in promoting lung squamous cell carcinoma progression and suggest that AP-1 and JNK inhibitors could be useful in treating high AP-1 lung squamous cell cancers.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE267nnn/GSE267597 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE267597 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1111911 ncbi.nlm.nih.gov/bioproject/PRJNA1111911 ↗
project · from NCBI GEO
- PubMed 41339492 pubmed.ncbi.nlm.nih.gov/41339492 ↗
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% · Genetics 68% · Genome sequencing 65%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE267597 | 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 (75%) |
| concepts[field].anzsrc:group:3105 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (68%) |
| 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:genome-sequencing | 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 |