Abstract 4773: DEAD Box 1 (DDX1) protects its RNA targets in cells exposed to oxidative stress
Bibliographic record
Abstract
Abstract DEAD box 1 (DDX1) belongs to the family of RNA helicases involved in all aspects of RNA metabolism, from transcription to transport, expression, and decay. DDX1 is overexpressed in a subset of retinoblastoma, neuroblastoma, and breast cancers. In breast cancer, the overexpression and cytoplasmic localization of DDX1 is correlated with poor prognosis. Cancer cells often exhibit high metabolic rates which can lead to genomic instability, oxidative stress, and endoplasmic stress. DDX1 is known to play a role in resolving genotoxic stress by participating in DNA double-strand break (DSB) repair. We propose that DDX1 also plays a key role as a stress response regulator in cells undergoing oxidative stress. When cells are exposed to oxidative stress, DDX1 is recruited to cytoplasmic stress granules (SGs). Although the exact function of SGs remains elusive, it is generally believed that tightly controlled SG assembly and disassembly are important for cell survival under stress. We found that while DDX1 is dispensable for SG assembly, depletion of DDX1 leads to impaired SG disassembly and hence, delayed stress recovery. Thus, DDX1 may play a role in stress resolution after the removal of stress conditions. To further understand the role of DDX1 in stress resolution, we performed RNA-immunoprecipitation followed by next-generation sequencing and identified DDX1-bound RNAs under normal and oxidative stress conditions. We found enhanced binding of DDX1 to its RNA targets in the presence of oxidative stress. Furthermore, we observed that DDX1 protects its target RNAs from degradation in the cytoplasm of cells undergoing oxidative stress. This RNA protection after stress exposure was more prominent in DDX1-overexpressing neuroblastoma cells, possibly explaining the faster stress recovery observed in these cells. Taken together, our results suggest that DDX1 plays a role in protecting cells from oxidative stress. This study may shed light on our understanding of cancer cell resistance to anticancer therapies. Citation Format: Mansi Garg, Roseline Godbout. DEAD Box 1 (DDX1) protects its RNA targets in cells exposed to oxidative stress. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4773.
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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) | 0.003 | 0.001 |
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".