Evaluating the impact reduced FBXO7 expression has on chromosome instability and cellular transformation in colorectal cancer pathogenesis
Bibliographic record
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed and second most lethal cancer in Canada. Therefore, understanding the genes and pathways driving CRC development is crucial to gain mechanistic insight that can be exploited in future therapies and consequently, decrease morbidity and mortality rates. Chromosome instability (CIN), or ongoing changes in chromosome numbers, is a predominant form of genome instability associated with ~85% of CRCs, suggesting it may be a key mechanism driving CRC oncogenesis. Moreover, CIN enables the acquisition of copy number alterations conferring selective growth, proliferation, and survival advantages, therefore CIN is often associated with cellular transformation. Despite these associations, the aberrant genes underlying CIN remain largely unknown. Recent preliminary screens of suspected CIN genes identified FBXO7 as a strong candidate for further study. FBXO7 encodes an F-box protein, a subunit of the SCF complex that normally targets specific protein substrates for proteolytic degradation by the 26S proteasome. Currently, the impact reduced FBXO7 expression has on CIN, cellular transformation and oncogenesis remains unknown. Thus, establishing the effects of diminished FBXO7 expression will shed new light on the underlying mechanisms of CIN. The current study seeks to evaluate the impact diminished FBXO7 expression has in malignant and non-malignant colonic epithelial cell contexts using complementary siRNA and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 approaches coupled with single-cell quantitative imaging microscopy (QuantIM) to assess changes in CIN-associated phenotypes. In doing so, QuantIM approaches determined that reduced FBXO7 expression induced increases in nuclear areas, micronucleus formation and frequencies of spreads with aberrant chromosome numbers. Collectively, this work identifies FBXO7 as a novel CIN gene with clinical implications that may contribute to CRC pathogenesis. Thus, this study is a first step towards gaining a novel understanding of the molecular origins of CIN and cellular transformation in CRC.
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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 | 0.001 | 0.001 |
| 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".