Abstract 1981: Histone demethyalase JMJD1A promotes the DNA damage response of prostate cancer cells
Bibliographic record
Abstract
Abstract DNA damage is a common feature of prostate cancer (PCa) therapies (e.g. radio-, chemo- and androgen deprivation therapies). Thus, the DNA damage response (DDR) is a key factor in determining the therapeutic response of PCa patients. JMJD1A regulates gene expression by demethylating H3K9. Here, we identified a new role for JMJD1A in the DDR of PCa cells. Inhibition of JMJD1A led to increased r-H2AX foci (marker for the double strand DNA breaks) in the non-irradiated cells, and the delayed clearance of r-H2AX foci in the irradiated cells. JMJD1A knockdown in PCa cells inhibited the DNA strand break repair in the reporter assays. We further found that phosphorylation and ubiquitination were key modifications that regulate the activity of JMJD1A in the DDR. Ectopic expression of the mutant JMJD1A at the phosphorylation or ubiquitination site attenuated the expression of DNA repair factors, DNA strand break repair, and PCa cell proliferation under irradiation and androgen deprivation conditions. Our results suggest that targeting JMJD1A may sensitize the response of PCa to the major anti-PCa therapies. Citation Format: Lingling Fan, Guihong Peng, Natasha Sahgal, Ladan Fazli, Martin Gleave, Yuji Zhang, Arif Hussain, Feyruz Rassool, Jianfei Qi. Histone demethyalase JMJD1A promotes the DNA damage response of prostate cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1981.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.014 | 0.003 |
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".