Omics · study · 2026
RAD21 reshapes H3K4me3 modification to drive lung adenocarcinoma progression by activating ERK1/2 signal
Listed in NCBI GEO
RAD21, the core unit of the cohesin complex, is involved in the transcriptional regulation of cells.
Description
The high-frequency copy number amplification of RAD21 is general in multiple cancer types and positively correlated with high mRNA levels, such as lung adenocarcinoma (LUAD). However, its role in LUAD is unclear.
We found that RAD21 is a poor prognostic factor for LUAD patients. Functionally, depletion of RAD21 using shRNAs impairs LUAD cell proliferation and metastatic ability. Transcriptome sequencing reveals that RAD21 loss inactivates epithelial-mesenchymal transition (EMT) and MAPK signaling pathways in LUAD cell lines, which can be rescued by exogenous RAD21.
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Pharmacologic ERK1/2 inhibition with specific inhibitor ulixertinib exhibits superior repression on the RAD21-driven high metastatic ability. Clinical exploration using specimens from LUAD patients further validates the correlation between RAD21 and the ERK1/2-EMT process. Taken together, our work reveals the regulatory relationship between RAD21-mediated epigenetic regulation and metastasis signaling cascade in LUAD.
The favorable therapeutic efficacy of ulixertinib in mouse models with lung metastasis provides a therapeutic rationale for ERK1/2 inhibition in RAD21-high LUAD.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE294nnn/GSE294135 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294135 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1248438 ncbi.nlm.nih.gov/bioproject/PRJNA1248438 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · RNA sequencing 65% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE294135 | 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |