Transcriptome Analysis Suggests PKD3 Regulates Proliferative Glucose Metabolism, Calcium Homeostasis and Microtubule Dynamics After MEF Spontaneous Immortalization
Bibliographic record
Abstract
Cell immortalization corresponds to a biologically relevant clinical feature that allows cells to acquire a high proliferative potential during carcinogenesis. In multiple cancer types, Protein Kinase D3 (PKD3) has often been reported as a dysregulated oncogenic kinase that promotes cell proliferation. Using mouse embryonic fibroblasts (MEFs), in a spontaneous immortalization model, PKD3 has been demonstrated as a critical regulator of cell proliferation after immortalization. However, the mechanisms by which PKD3 regulates proliferation in immortalized MEFs require further elucidation. Using a previously validated Prkd3-deficient MEF model, we performed a poly-A transcriptomic analysis to identify putative Prkd3-regulated biological processes and downstream targets in MEFs after spontaneous immortalization. To this end, differentially expressed genes (DEGs) were identified and further analyzed by gene ontology (GO) enrichment and protein–protein interaction (PPI) network analyses to identify potential hub genes. Our results suggest that Prkd3 modulates proliferation through the regulation of gene expression associated with glucose metabolism (Tnf, Ucp2, Pgam2, Angptl4), calcium homeostasis and transport (Calcr and P2rx7) and microtubule dynamics (Stmn2 and Map10). These candidate processes and associated genes represent potential mechanisms involved in Prkd3-induced proliferation in spontaneously immortalized cells as well as clinical targets in several cancer types.
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How this classification was reachedexpand
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".