Effects of γ‐glutamyl hydrolase modulation on CpG promoter DNA methylation and gene expression in human colon cancer cells
Bibliographic record
Abstract
γ‐Glutamyl hydrolase (GGH) plays an important role in folate homeostasis by catalyzing hydrolysis of polyglutamylated folate into monoglutamates, thereby facilitating export of folate from cell. We investigated whether GGH modulation would affect CpG promoter methylation and gene expression profiles in human HCT116 colon cancer cells. Illumina HT‐12 and Infinium Methylation assay were performed in the GGH‐modulated HCT116 cells, and Ingenuity Pathway Analysis was used for functional analysis. The mRNA expression of selected genes, expression of which was epigenetically regulated was confirmed by qRT‐PCR. We identified 153 differentially expressed genes (most involved pathways: cellular movement and cell death) associated with GGH overexpression, and 321 differentially expressed genes (most involved pathways: cell death and cell cycle) associated with GGH inhibition. 905 and 1869 genes showed altered CpG promoter methylation associated with GGH overexpression and inhibition, respectively. An integrated analysis revealed 5 and 16 genes, expression of which was regulated by CpG promoter methylation changes associated with GGH overexpression and inhibition, respectively. Thus, GGH modulation can affect differential gene expression and CpG promoter DNA methylation involved in important biological pathways and some of the observed altered 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".