Faculty Opinions recommendation of Sirtuin 6 inhibits colon cancer progression by modulating PTEN/AKT signaling.
Bibliographic record
Abstract
Decreased expression of the tumor suppressor sirtuin 6 (SIRT6) protein plays a role in tumorigenesis. The aim of this study was to investigate the effects of SIRT6 and its underlying mechanism in colon cancer progression. As shown by immunohistochemistry, Western blotting, and the real-time polymerase chain reaction (RT-PCR), SIRT6 expression was down-regulated in colon cancer tissues and different colon cancer cell lines, and down-regulation of SIRT6 showed a negative correlation with the overall survival of colon cancer patients. To assess the effects of SIRT6 on cell proliferation, apoptosis, invasion, and migration, 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, transwell, and wound healing assays were carried out, respectively. Results demonstrated that over-expression of SIRT6 inhibited cell proliferation, invasion, and migration and enhanced cell apoptosis. Co-immunoprecipitation (Co-IP) and Western blotting showed that up-regulation of SIRT6 increased the combined quantity of PTEN with SIRT6 proteins, and promoted the expression of PTEN and PIP2, as well as the stability of PTEN. SIRT6 also reduced the ubiquitination of PTEN and decreased protein levels of AKT1, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), mTOR, cyclin d1, and c-myc. In addition, compared with cells over-expressed SIRT6, cell apoptosis was repressed and cell proliferation and tumorigenesis were enhanced in cells with SIRT6 over-expression and PTEN knockdown. In conclusion, the present study confirms that SIRT6 functions as a tumor suppressor gene in colon cancer by modulating PTEN/AKT signaling, which may provide a novel target for the treatment of colon cancer.Copyright © 2018. Published by Elsevier Masson SAS. PMID: 29957460
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.284 | 0.113 |
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".