Omics · study · 2026
Ro 08-2750 increases radiation-induced cytotoxicity in DLBCL by dysregulating DNA damage response
Listed in NCBI GEO
Introduction Current research efforts attempt to increase therapy efficacy in diffuse large B-cell lymphoma (DLBCL).
Description
Here, we evaluated the effects of small molecule inhibitor Ro 08-2750 on therapy-induced cytotoxicity in DLBCL. Material and methods First, we established Ro 08-2750 treatment in DLBCL by verifying cell toxicity via cell viability and colony formation assays.
In a next step, functional effects reducing cell viability, e.g. cell cycle dysregulation and apoptosis, were analyzed via flow cytometry. Then, we evaluated effects of Ro 08-2750 on cytotoxic therapy in cell viability and colony formation assays. After confirming an increase in irradiation-induced DNA damage via γH2AX assay, an immunoblot-based assay was used to detect changes in DNA damage response.
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Lastly, we analyzed Ro 08-2750-induced changes in gene and protein expression via RT-qPCR, RNA sequencing, western blot and proteomic analysis. Results Ro 08-2750 reduces cell viability dose-dependently in DLBCL. Functionally, the decrease in cell viability is combined with a cell cycle dysregulation, specifically an increase in S phase with reduced G2/M phase, and an increase in apoptosis.
DNA synthesis is reduced during S phase. Assessing the therapeutical relevance, Ro 08-2750 sensitized DLBCL cell lines to irradiation but not chemotherapy and increased irradiation-induced double strand breaks. We found a dysregulation in CHK2 phosphorylation.
Moreover, Ro 08-2750 dysregulated DNA damage response in genomic and proteomic analysis. Conclusion We identified Ro 08-2750 as a potential radiosensitizer in DLBCL. Therefore, our results indicate the potential therapeutical benefit of targeting RNA binding proteins
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301732 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301732 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1287496 ncbi.nlm.nih.gov/bioproject/PRJNA1287496 ↗
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 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE301732 | 13 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 (75%) |
| 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 |