Omics · study · 2026
miRNA-mediated cell-to-cell communications boost DNA repair during the Radioadaptative Response in human fibroblasts
Listed in NCBI GEO
The radioadaptive response is a phenomenon in which cells exposed to a low priming dose of ionizing radiation develop increased resistance to a subsequent higher challenging dose for a period of time.
Description
Little is known of the molecular components of this response. Here, we focus on determining if during the RAR there are changes in the Homologous Recombination, the more faithful DNA Double Strand break repair pathway.
Using immortalized fibroblasts as a model system, we demonstrate that primed cells exhibit faster DNA resection, the initial step of homologous recombination, following a challenging dose, as indicated by RPA foci kinetics. We further establish that the stimulation of resection during the RAR is mostly established and maintained through cell-to cell communication via extracellular vesicles. Indeed, media exchange experiments demonstrated that soluble factors in the conditioned media were sufficient to fully recapitulate the RAR effect.
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RNA analyses of extracellular vesicles cargo revealed differential expression of miRNAs, particularly miR-126-3p and miR-451a, which we show play crucial roles in modulating the RAR. Notably, inhibition of miR-451a was sufficient to induce the RAR in cells that typically do not exhibit this response. Finally, we identified the p38-CCAR2 axis as a critical regulator of the RAR-mediated DNA end resection boost. p38 activation following priming irradiation block CCAR2 activity, facilitating a more efficient repair process.
Collectively, our findings elucidate a novel mechanism by which EV-mediated communication and specific miRNA signaling enhance HR efficiency in response to radiation, offering insights into potential therapeutic applications in radiotherapy.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293977 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293977 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1247519 ncbi.nlm.nih.gov/bioproject/PRJNA1247519 ↗
project · from NCBI GEO
- PubMed 42554161 pubmed.ncbi.nlm.nih.gov/42554161 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE293977 | 15 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[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 |