Inhibition of miR-182-5p protects cardiomyocytes from hypoxia-induced apoptosis by targeting CIAPIN1
Bibliographic record
Abstract
Myocardial infarction (MI), a type of ischemic heart disease, is generally accompanied by apoptosis of cardiomyocytes. MicroRNAs play the vital roles in the development and physiology of MI. Here, we established a downregulation model of miR-182-5p in H9c2 cells under hypoxic conditions to investigate the potential molecular mechanisms for miR-182-5p in hypoxia-induced cardiomyocyte apoptosis (HICA). RT-qPCR indicated that miR-182-5p levels exhibit a time-dependent increase in the rate of apoptosis induced by hypoxia. The results from the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) assays indicated that cardiomyocyte injury noticeably increased after exposure to hypoxia. Meanwhile, hypoxia dramatically increased the apoptosis rate [which was reflected in the results from the annexin V - propidium iodide (PI) assay], enhanced caspase-3 activity, and reduced the expression of Bcl-2. Downregulation of miR-182-5p can significantly reverse hypoxia-induced cardiomyocyte injury or apoptosis. Importantly, bioinformatic analysis and dual-luciferase reporter assay revealed that CIAPIN1 (cytokine-induced apoptosis inhibitor 1) was a direct functional target of miR-182-5p, and that inhibition of miR-182-5p can lead to an increase in CIAPIN1 expression at both the mRNA and protein levels. Furthermore, the knockdown of CIAPIN1 with small interfering RNAs (siRNAs) efficiently abolished the protective effects of miR-182-5p inhibitor on HICA, demonstrating that miR-182-5p plays a pro-apoptotic role in cardiomyocytes under hypoxic conditions by downregulating CIAPIN1. Collectively, our results demonstrate that miR-182-5p may serve an underlying target to prevent cardiomyocytes from hypoxia-induced injury or apoptosis.
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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) | 0.000 | 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) | 0.000 | 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".