Omics · study · 2026
Effect of CRISPRi-based depletion of IREB2, MRGBP, and PAX7 on gene expression in A549 dCas9-KRAB cells
Listed in NCBI GEO
The DNA damage response (DDR) is a sophisticated network of cellular pathways whose perturbation leads to genome instability and is a key hallmark of oncogenesis.
Description
Through orthogonal CRISPRi screens with diverse DDR inhibitors (DDRi) we find a strong chemical-genetic interaction between loss of activity of the peroxiredoxin PRDX1 and all tested inhibitors through a mechanism involving iron availability mediated by an MRGBP-PAX7-IREB2 axis.
Loss of IREB2 is believed to reduce free iron levels in cells by repressing translation of the transferrin receptor, and therefore iron uptake, and by promoting ferritin translation to increase iron storage capacity. As PAX7 and MRGBP are both associated with gene expression, we performed bulk RNA-seq in A549 dCas9-KRAB cells expressing sgRNAs targeting IREB2, PAX7, and MRGBP. Strikingly, in all three instances, IREB2 was one of the most downregulated genes.
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In addition, knockdown of PAX7 led to downregulation of MRGBP and knockdown of MRGBP to downregulation of PAX7. Together, these data indicate that PAX7 and MRGBP cooperate to regulate expression of IREB2 and demonstrate the MRGBP-PAX7-IREB2 as a driver of resistance to DDRi through convergence on IREB2 expression and thus the control of cellular iron levels.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320129 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320129 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1426422 ncbi.nlm.nih.gov/bioproject/PRJNA1426422 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE320129 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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[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 |