miR-526b dysregulates glucose metabolism via the COX2/EP4 pathway
Bibliographic record
Abstract
Abstract Introduction: Breast cancer (BRCA) remains a primary global health concern, with ongoing research focused on early detection and improving treatment methods. Moving forward, it is crucial to understand cancer cell metabolism and its impact on tumor growth and metastasis. This study aims to identify potential BRCA markers related to glucose metabolism for targeted therapy, focusing on the role of miR-526b. miR-526b promotes BRCA phenotypes, including migration, invasion, hypoxia, angiogenesis, and metastasis. Further, cell-free secretion of miR-526b-high BRCA tumor cells can alter the tumor microenvironment. This study will investigate the role of miR-526b in the dysregulation of glucose metabolism. Methods: We used two immortalized BRCA cell lines, MCF7 and SKBR3, and stable miR-526b overexpressed cells MCF7-miR526b and SKBR3-miR526b and a naturally miR-526b high cell line MCF7-COX2 for in vitro assays. We measured ATP production, oxygen consumption rate, and extracellular acidification rate. We used glycolysis and OXPHOS inhibitors to measure metabolic plasticity induced by miR-526b. A COX-2 inhibitor and EP4 antagonist were used to alter miR-526b-induced functions. For RNA and protein measurement, we used qRT-PCR and western blots. In silico analysis with online datasets validated our findings in human BRCA. Results: In silico analysis showed that genes related to glycolysis and oxidative phosphorylation (OXPHOS) are enriched in human breast cancer tissues. Overexpression of miR-526b promotes cell proliferation and ATP production. It also contributes to the upregulation of LDHA and PDHA1, which determine the fate of the glycolytic product pyruvate, either producing lactate or entering the TCA cycle to promote OXPHOS. miR-526b overexpressing cells demonstrated increased metabolic plasticity and decreased adverse effects following treatment with glycolysis and OXPHOS inhibitors, showing increased survival and proliferation. The metabolic dysregulation induced by miR-526b, including increased proliferation, ATP production, and marker expression, can be reversed using a COX2 inhibitor and EP4 antagonist. Conclusion: miR-526b promotes increased glucose metabolism and ATP production, supporting increased growth and division of BRCA cells. It also increases metabolic plasticity, improving cells' ability to thrive in a complex and heterogeneous tumor microenvironment. The dysregulation observed with miR-526b can be reversed by targeting the COX2/EP4 pathway.
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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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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".