Elevated ZNF704 expression is associated with poor prognosis of uveal melanoma and promotes cancer cell growth by regulating AKT/mTOR signaling
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
BACKGROUND: Uveal melanoma (UM) is the most common intraocular malignancy in adults, with a poor survival prognosis. To date, limited understanding of UM's molecular mechanisms constitutes an obstacle to developing effective therapy. In this study, we examined key regulators mediating UM progression and their clinical relevance. METHODS: Transcriptomics of UM patients and cells were analyzed via RNA sequencing and bioinformatic analysis. Zinc finger protein 704 (ZNF704) was identified as prognosis-related biomarker for UM based on clinical characteristics and RNA-seq data from The Cancer Genome Atlas (TCGA). Gene expression was knocked down by specific shRNAs/siRNAs and overexpressed by transfection with plasmids inserted with investigated gene cDNA. Cell proliferation, viability and invasion abilities were determined by CCK8, colony formation and transwell assays, respectively. For cell cycle and apoptosis, cells were PI or PI/Annexin V-APC stained and analyzed by flow cytometry. Standard immunoblotting and quantitative RT-PCR were employed to assess the mRNA and protein abundance. To determine tumor growth in vivo, 4-week-old BALB/c-nu immune-deficient nude mice were inoculated with tumor cells. RESULTS: Analysis of differential expressed genes (DEGs) and survival analysis identified ZNF704 as a novel biomarker of UM. Prognostic analysis indicated ZNF704 as an independent predictor of UM overall survival. Expression of ZNF704 is elevated in UM tissues relative to adjacent normal choroid tissues. Knockdown of ZNF704 suppressed the growth and migration of UM cells and vice versa. In addition, expression of ZNF704 arrest UM cells at G0/G1 phase and inhibit cell apoptosis. RNA sequencing analysis indicated that SORBS3 were dysregulated after ZNF704 downregulation. Gene Set Enrichment Analysis (GSEA) revealed that upon ZNF704 knowndown, genes related with PI3K/AKT/mTOR, EMT and metastasis are enriched. Mechanistically, ZNF704 activates AKT/mTOR/glycolysis signaling pathway in UM cells. Moreover, expression of SORBS3 is downregulated by ZNF704 and knockdown of SORBS3 restored tumor cell viability in ZNF704 silenced cells. CONCLUSIONS: ZNF704 predicts poor prognosis of UM and exhibit pro-oncogenic effect in UM progression in vivo and in vitro, mediated through AKT/mTOR signaling pathway and suppression of SORBS3 expression.
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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 | 0.001 |
| 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) | 0.000 | 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