A Novel Protein NAB1‐356 Encoded by circRNA circNAB1 Mitigates Atrial Fibrillation by Reducing Inflammation and Fibrosis
Bibliographic record
Abstract
Atrial fibrillation (AF) is a common arrhythmia with irregular atrial electrical activity. Circular RNAs (circRNAs) are key regulators in tissue homeostasis, yet their role in AF remains unclear. Here, we investigated the expression and function of circNAB1 in AF using high-throughput sequencing and functional assays in circNAB1 transgenic mice. We identified circNAB1 as a significantly downregulated circRNA in AF patient specimens. Silencing circNAB1 promoted collagen deposition and inflammation, whereas overexpression reduces atrial fibrosis and AF susceptibility in mice, consistent with results observed in human atrial tissues. Mechanistically, circNAB1 translates into a novel protein, NAB1-356, which is highly expressed in human cardiac hypertrophy. NAB1-356 interacts with EGR1 as NAB1 does, decreasing fibrosis and inflammation in the atrium. Furthermore, NAB1-356 also regulates transcription factor Runx1 and Gadd45b transcription, exerting regulatory effects on cytokine expression and fibrosis. Targeting EGR1, Gadd45b, and Runx1 by circNAB1 or siRNAs attenuate AF incidence and cardiac remodeling, suggesting potential therapeutic strategies for AF management. Delivery of circNAB1 improves AF conditions in LKB1 knockout mice, further highlighting its anti-arrhythmic potential. Our findings elucidate the mechanistic role of circNAB1 in AF pathogenesis and suggest its therapeutic implications for cardiac remodeling-associated disorders.
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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 | 0.001 |
| 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".