DUSP4 inhibits autophagic cell death in PTC by inhibiting JNK–BCL2–Beclin1 signaling
Bibliographic record
Abstract
Dual specificity phosphatase 4 (DUSP4) is a prognostic marker and potential target of papillary thyroid carcinoma (PTC); however, the molecular mechanism underlying DUSP4-regulated PTC carcinogenesis is unknown. DUSP4 is a negative regulator of the autophagy promoter, JNK. This study explored the relationship between DUSP4 and JNK-mediated autophagic cell death in PTC, and the roles of DUSP4 in PTC using gain-of-function and loss-of-function assays. In addition, we further identified the significance of the JNK-BCL2-Beclin1-autophagy signaling pathway on DUSP4-regulated PTC carcinogenesis by combining knockdown of DUSP4 with a JNK-specific inhibitor (SP600125). We found that knockdown of DUSP4 promoted the phosphorylation of JNK and BCL2 in PTC cells, and enhanced the release of Beclin1 from the BCL2-Beclin1 complex. Knockdown of DUSP4 promoted autophagy and the death of PTC cells. The death and autophagy enhanced by knockdown of DUSP4 was reversed by the JNK inhibitor. We further extended the in-vitro experiments by subcutaneously injecting nude mice with K1 cells transfected with DUSP4-silencing vector. In-vivo assays showed that knockdown of DUSP4 not only inhibited tumor growth, but also promoted the phosphorylation of JNK and BCL2 and the expression of LC3II. In conclusion, DUSP4 inhibits BCL2-Beclin1-autophagy signaling by negatively regulating JNK activity, thus inhibiting PTC oncogenesis. The data from this study contribute to the prevention and cure of PTC.
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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".