Role of the transcription factor Yin Yang 1 in non‐small cell lung cancer
Bibliographic record
Abstract
Background Lung cancer is the most prevalent cancer type worldwide by both diagnosis and mortality, with non‐small cell lung cancers (NSCLCs) featuring as the most common histological subtype, the latter of which consists of squamous (epidermoid), adenocarcinoma, and large cell carcinoma. Rates of lung cancer will continue to rise owing to high levels of cigarette consumption and aging populations. Despite increased surgical resection rates, optimization of chemo‐radiotherapy and the introduction of targeted therapies, the treatment outcome for NSCLC remains poor. Therefore, identification of new molecular targets, which are essential for proliferation of tumor cells, will benefit both treatment and chemoprevention of NSCLC. The Yin Yang 1 (YY1) transcription factor has a pivotal role in normal biological processes such as development, differentiation, replication and cell proliferation exerting its effects on a huge number of genes involved in these processes. Due to its functions during lung morphogenesis, we hypothesize that YY1 is overexpressed and contributes to the pro‐proliferative and anti‐apoptotic phenotype of cancerous cells. Method/Results Expression level of YY1 was first examined by immunohistochemistry (n=5) and western blot (n=11) in resected tumor tissue of NSCLC patients (stages I–III) and compared to adjacent non‐cancerous lung tissue. Results showed that YY1 expression is significantly increased in squamous cell carcinoma and adenocarcinoma of the lung. A greater proliferation rate (Ki67 labeling) was associated with strong YY1 expression in these human lung tumors. In vitro, transient transfection experiments with A549 lung adenocarcinoma cells showed that depletion of YY1 levels by short interfering RNA reduced proliferation (Ki67 labeling and MTT assay, p<0,001), resistance to apoptosis (Annexin V assay, cleaved caspase‐3 expression, p<0,05) and migration (wound healing assay, p<0,001). In addition, YY1 knockdown improved in vitro NSCLC sensitivity to Etoposide/Cisplatin, two chemotherapeutic agents. Conclusion Taken together, these findings suggest that up‐regulation of YY1 plays an important role in the development of lung cancer. Susceptibility of YY1‐depleted A549 cells and YY1 heterozygous mice to induce tumors is currently under investigation. Analysis of YY1 expression in a larger cohort of patients may reveal prognostic information and deserves further study. Support or Funding Information None
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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) | 0.001 | 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".