A243 FUNCTIONAL ROLES OF NCOR1 AND CHD8 PROTEIN INTERACTION IN HUMAN COLORECTAL CANCER CELLS.
Bibliographic record
Abstract
The nuclear receptor co-repressor 1 (NCOR1) is a protein with transcriptional repression activity interacting with nuclear receptors. NCOR1 is involved in targeting gene transcription related to intestinal inflammatory response and colorectal cancer. We have previously identified the chromatin helicase DNA binding 8 (CHD8) protein as a potential interactor of NCOR1. CHD8 is a DNA helicase that functions as a transcription repressor by remodeling chromatin structure. To investigate the functional and biological roles of CHD8 interaction with NCOR1 in colorectal cancer. HT-29 and Caco-2/15 cell lines were depleted in NCOR1 or CHD8 by RNAi. Cell proliferation of the generated cell lines was measured by cell counts. Overall changes in transcriptome was determined by high-throughput RNA sequencing. Chromatin immunoprecipitation (ChIP) was performed with the use of a specific CHD8 antibody. Multiple HA and V5 epitope-tagged domain fragments of NCOR1 and CHD8 were generated for interaction assays. Depletion of NCOR1 in HT-29 and Caco-2/15 cells led to a strong reduction of cell proliferation, while depletion of CHD8 led to a less robust effect. High-throughput RNA sequencing identified more than 60 common genes for which the expression was modulated in both NCOR1 and CHD8 depleted HT-29 and Caco-2/15 cell populations. Among these modulated genes, the Brain Derived Neutrophic Factor (BDNF), known to be involved in cancer cell motility, was identified as a common gene target for both NCOR1 and CHD8. ChIP with the use of a CHD8 specific antibody was optimized in colorectal cancer cell lines to monitor the level of CHD8 chromatin occupancy among the identified genes. Finally, various tagged constructs representative of specific domains of NCOR1 and CHD8 have been generated and validated by Western blot. Interactions strategies are currently undergoing to functionally validate NCOR1 and CHD8 biological link. NCOR1 and CHD8 interact together, affect common genes and negatively influence colorectal cancer cell proliferation. Identification of the specific nature of this interaction will highlight novel strategies to disrupt NCOR1-CHD8 interaction in order to regulate colorectal cancer cell proliferation. CIHR
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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) | 0.004 | 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".