Cell Cycle Regulator ING4 Is a Suppressor of Melanoma Angiogenesis That Is Regulated by the Metastasis Suppressor BRMS1
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
ING4 has been previously shown to play important roles in regulating apoptosis, cell cycle progress, cell migration, and invasion. In this study, we investigated the impact of ING4 on melanoma angiogenesis. ING4 overexpression strongly suppressed the growth of human umbilical vein endothelial cells (HUVEC) and their ability to form tubular structure in vitro. We also found that ING4 inhibits interleukin-6 (IL-6) at both mRNA and protein levels through suppressing NF-κB activity. Knockdown of endogenous ING4 resulted in enhanced HUVEC growth and IL-6 expression. Our in vivo studies using nude mice confirmed that ING4 inhibited blood vessel formation and the recruitment of CD31-positive cells in matrigel plugs. Furthermore, we found that expression of ING4 was induced by BRMS1, a metastasis suppressor that inhibits melanoma angiogenesis through inhibiting NF-κB activity and IL-6 level as well. Further experiments showed that ING4 knockdown abrogated the suppressive effect of BRMS1 on HUVEC growth, whereas ING4 overexpression inhibited BRMS1 knockdown-induced angiogenesis, indicating that ING4 is a downstream target of BRMS1 in regulating tumor angiogenesis. Collectively, our findings indicate that ING4 is induced by BRMS1 and that it inhibits melanoma angiogenesis by suppressing NF-κB activity and IL-6 expression. Restoration of ING4 function offers a potential new strategy for the treatment of human melanoma.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| 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 it