Impact of the epigenetic modulator BORIS on sensitivity of melanoma cells to UV-induced DNA damage.
Bibliographic record
Abstract
e21077 Background: Cutaneous melanomas display considerably higher mutational load compared to other solid tumors, mainly due to DNA damage and absent/defective repair. Chromatin organization plays an important role in these processes, with open chromatin conferring a higher sensitivity to DNA damage. BORIS is an epigenetic modifier that is correlated with open chromatin and is abnormally expressed in primary and metastatic melanoma. Here we set out to obtain a better understanding of BORIS’s role in chromatin organization and DNA damage in melanoma. Methods: A panel of melanoma cell lines was selected and BORIS mRNA expression was determined using qPCR. Cellular localization of BORIS was assessed by immunofluorescence. Ectopic BORIS expression was established exploiting a doxycycline inducible expression vector and proliferation was assessed using crystal violet and Hoechst staining. DNA damage was induced by exposure to 60 J/m2 UVC followed by apoptosis and cell cycle analysis using flow cytometry. Results: We confirmed aberrant BORIS expression in 61% of our melanoma cell line panel and observed nuclear BORIS localization in areas of low chromatin density. Forced expression of BORIS in BORIS low/intermediate cell lines resulted in a significant reduction in cell growth and increased cell death. Interestingly, BORIS overexpressing cells exposed to UV irradiation displayed a higher degree of cell cycle alterations and increased level of apoptosis compared to BORIS low/intermediate cells. Conclusions: Our results demonstrate that BORIS is increased in melanoma, localized in areas of open chromatin, and increased sensitivity to UV-induced DNA damage. Taken together, this indicates a role for BORIS in directing the chromatin state into a more open conformation, allowing increased sensitivity to DNA damage. Currently, we are analyzing DNA damage in BORIS overexpressing cells and are further investigating BORIS’s role in directing chromatin state by exploiting ATAC-seq and ChIP-seq for various epigenetic marks.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".