MicroRNA miR-378-3p is a novel regulator of endothelial autophagy and function
Bibliographic record
Abstract
Autophagy is a highly conserved cellular process in which cytoplasmic materials are internalized into an autophagosome that later fuses with a lysosome for their degradation and recycling. MicroRNAs (miRNAs) are integral regulators in various cellular processes including autophagy and endothelial function. Accordingly, we hypothesize that miRNA, miR-378-3p, is an essential regulator of endothelial autophagy and endothelial function. MiR-378-3p expression was measured following inhibition and activation of autophagy in endothelial cells. A gain- or loss-of function approach was employed to either overexpress or inhibit the expression of miR-378-3p, respectively, in cultured endothelial cells, and markers of autophagy and indices of endothelial function, such as proliferation, migration and tube forming potential were measured. Inhibition and activation of autophagy up- and down-regulated the expression of miR-378-3p, respectively. Furthermore, miR-378a-3p overexpression was associated with impaired autophagy indicated by a reduced LC3-II/LC3-I ratio, and endothelial function indicated by increased proliferation associated with reduced p21 expression, reduced angiogenic potential and increased migration, which were associated with reduced expression of endothelial nitric oxide synthase (eNOS), an essential regulator of endothelial function. Accordingly, miR-378a-3p inhibition was associated with reduced cell proliferation, migration and increased eNOS in endothelial cells. Apoptosis was not affected in cells transfected with antagomir. Using in silico approach, Protein Disulfide Isomerase Family A Member 4 (PDIA-4) was identified and confirmed as a target of miR-378-3p. PDIA-4 expression was significantly reduced or enhanced in miR-378-3p-overexpressing or -silenced endothelial cells, respectively. Our findings show an inverse relationship between miR-378-3p and endothelial autophagy and function, providing a novel insight about the epigenetic regulation of these processes.
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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) | 0.001 | 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".