TRIM3 modulates cisplmatin-resistant of cervical squamous cell carcinoma via endoplasmic reticulum stress signaling in vitro
Bibliographic record
Abstract
TRIM3 is widely recognized as a tumor suppressor gene. However, its precise role in cervical squamous cell carcinoma (CESC) remains elusive. Here, we observed a significant decrease in the expression of TRIM3 in CESC cells. Overexpression of TRIM3 suppresses cell proliferation and clonal formation. Through the establishment of cisplatin (cDDP)-resistant CESC cell lines, we discovered that the expression of TRIM3 was further downregulated in cDDP-resistant cells, while overexpression of TRIM3 enhanced cellular sensitivity to cDDP. Mechanistic investigations revealed that TRIM3 directly interacts with GRP78, a crucial protein involved in endoplasmic reticulum stress (ERS) pathway, promoting its ubiquitination degradation. Under cDDP treatment, the overexpression of TRIM3 in cDDP-resistant cells suppressed cell proliferation and downregulated the expression of drug-resistant genes, while simultaneously enhancing the activation of apoptosis signaling pathways. However, co-expression of TRIM3 and GRP78 restored cellular sensitivity to cDDP back to normal levels. Consequently, overexpressing TRIM3 in drug-resistant cells facilitates PERK activation and subsequent induction of apoptosis through inhibition of GRP78, ultimately suppressing drug resistance and inducing apoptosis in CESC cells. In conclution, our study suggests that the TRIM3/GRP78 axis regulates cDDP resistance in CESC cells by modulating the downstream apoptotic pathway of ERS.
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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) | 0.001 | 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".