miR-526b enhances glucose metabolism in breast cancer cells, an effect reversed by targeting the COX-2/EP4 pathway
Bibliographic record
Abstract
INTRODUCTION: Cancer cells reprogram metabolic pathways to meet energy demands and sustain rapid growth, a hallmark of malignancy. Identifying molecular signatures underlying these changes can aid in early detection and inform targeted therapies. miR-526b has been shown to promote migration, invasion, angiogenesis, and metastasis, yet its role in dysregulated glucose metabolism remains underexplored. METHODS: We used MCF7 (Luminal A) and SKBR3 (HER2-Enriched) breast cancer cell lines, which exhibit distinct metabolic characteristics, to study miR-526b's impact on metabolic marker expression, ATP production, oxygen consumption rate, and extracellular acidification. Cells were treated with glycolysis inhibitor 2 Deoxy-D-Glucose (2DG) or ox-phos inhibitor Oligomycin (OM) to measure dependence on glycolysis or oxidative phosphorylation. Stable transfection was used to overexpress miR-526b in MCF7 and SKBR3 cell lines, and miRNA inhibitors were used to inhibit miR-526b in MCF7-COX2 cells, comparing its effects across subtypes. Targeted inhibition of EP4 with a specific antagonist (EP4A) RQ-15986 (CJ-042794) was done in aggressive MCF7-COX2 cells to test the involvement of COX-2/EP4. RESULTS: SKBR3 exhibits an enhanced glycolytic phenotype, while MCF7 demonstrates increased ox-phos metabolism. Overexpression of miR-526b amplified these inherent metabolic properties, increasing ATP production and proliferation in both cell lines. miR-526b enhanced ox-phos activity in MCF7, reducing sensitivity to glycolysis inhibition, whereas it amplified glycolytic metabolism in SKBR3, reducing sensitivity to ox-phos inhibition. Overexpression of COX-2 in MCF7 replicated the metabolic effects of miR-526b. Inhibition of miR-526b in MCF7-COX2 cells enhances HK2 and GLUT1 expression, but did not significantly alter cell proliferation or cell viability. Targeting the COX-2/EP4 axis with a selective EP4A reversed the transcriptomic changes induced by miR-526b, but did not reduce the increased proliferation observed in MCF7-COX2. CONCLUSION: miR-526b enhances inherent metabolic characteristics of breast cancer cell lines, increasing ATP production, proliferation, and resistance to metabolic inhibitors. Targeting the COX-2/EP4 axis mitigated some of the effects induced by miR-526b, but it did not normalize cell behavior, highlights the complex regulation of glucose metabolism in breast cancer and underscores the need for combination therapy strategies.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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".