Cardiac‐specific overexpression of miR‐122 induces mitochondria‐dependent cardiomyocyte apoptosis and promotes heart failure by inhibiting Hand2
Bibliographic record
Abstract
MicroRNA-122 (miR-122) is one of several microRNAs elevated in heart failure patients. To investigate the potential role and mechanism of miR-122 in heart failure, we constructed a transgenic mouse overexpressing miR-122 in the heart. This mouse exhibited cardiac dysfunction (as assessed by transthoracic echocardiography), morphological abnormalities of the heart and cardiomyocyte apoptosis characteristic of heart failure. Mechanistically, we identified the Hand2 transcription factor as a direct target of miR-122 using a dual-luciferase reporter assay. In Tg-miR-122 mice and H9C2 cells with miR-122 mimics, we detected apoptosis and increased expression of dynamin-related protein-1 (Drp1). This effect was blocked with prior knockdown of Hand2 in vitro. Our work suggests that miR-122 causes cardiomyocyte apoptosis by inhibiting Hand2 and consequently increasing Drp1-mediated mitochondrial fission. Such a mechanism likely contributes to heart failure and so modulating this pathway could be therapeutically valuable against heart failure.
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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 | 0.001 |
| 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".