Effects of folylpolyglutamate synthase modulation on CpG promoter DNA methylation and gene expression in human colon cancer cells
Bibliographic record
Abstract
Folylpolyglutamate synthase (FPGS) facilitates intracellular retention of folate by polyglutamylation, thereby playing a critical role in folate homeostasis. We investigated whether FPGS modulation would affect CpG promoter methylation and gene expression profiles in human HCT116 colon cancer cells. Illumina HT‐12 and Infinium Methylation assay were used, and functional analysis was performed by Ingenuity Pathway Analysis. We validated mRNA expression of selected genes by qRT‐PCR. 2897 genes (most involved pathways: cell cycle and DNA replication, recombination, and repair) were differentially expressed in the FPGS‐overexpressed cells, while 359 genes (most involved pathways: cell death and cell cycle) were differentially expressed in the FPGS‐inhibited cells. 864 and 626 genes showed altered CpG promoter methylation associated with FPGS overexpression and inhibition, respectively. An integrated analysis revealed 65 and 6 differentially expressed genes involved in cell cycle, cell death, and cell‐to‐cell signaling and interaction, expression of which was regulated by CpG promoter methylation changes associated with FPGS overexpression and inhibition, respectively. FPGS modulation can affect differential gene expression and CpG promoter methylation involved in important biological pathways, and some of the observed differential gene expression appear to be epigenetically regulated. Grant Funding Source : CIHR Fund 14126
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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 | 0.000 |
| 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".