Dependence of p53-deficient cells on the DHX9 DExH-box helicase
Bibliographic record
Abstract
// Teresa Lee 1 , Jerry Pelletier 1, 2, 3 1 Department of Biochemistry, McGill University, Montreal, Quebec, H3G 1Y6, Canada 2 Department of Oncology, and McGill University, Montreal, Quebec, H3G 1Y6, Canada 3 Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada Correspondence to: Jerry Pelletier, email: jerry.pelletier@mcgill.ca Keywords: DHX9, helicase, p53, drug target, apoptosis Received: September 20, 2016 Accepted: February 21, 2017 Published: March 03, 2017 ABSTRACT DHX9 is a DExH-box helicase family member with key regulatory roles in a broad range of cellular processes. It participates at multiple levels of gene regulation, including DNA replication, transcription, translation, RNA transport, and microRNA processing. It has been implicated in tumorigenesis and recent evidence suggests that it may be a promising chemotherapeutic target. Previous studies have determined that DHX9 suppression elicits an apoptotic or senescence response by activating p53 signaling. Here, we show that DHX9 inhibition can also have deleterious effects in cells lacking functional p53. Loss of DHX9 led to increased cell death in p53-deficient mouse lymphomas and HCT116 human colon cancer cells, and G0/G1 cell cycle arrest in p53-deficient mouse embryonic fibroblasts. Analysis of mRNA levels for p53 transcriptional targets showed that a subset of p53 targets in the p53-null lymphomas and HCT116 cells were activated despite the absence of functional p53. This implies an alternative pathway of DHX9-mediated activation of cell death and cell cycle arrest in p53-deficient cells and supports the feasibility of targeting DHX9 in p53-deficient tumors.
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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) | 0.002 | 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".