lncRNA GCAT1 is involved in premature ovarian insufficiency by regulating p27 translation in GCs via competitive binding to PTBP1
Bibliographic record
Abstract
Dysfunction of granulosa cells (GCs) leading to follicle atresia has been extensively studied as a major cause of premature ovarian insufficiency (POI), but the regulatory role of long non-coding RNAs (lncRNAs) in this process is still poorly understood. Here, we show that the lncRNA LINC02690 or GCAT1 (granulosa cell-associated transcript 1) is downregulated in GCs from patients with biochemical POI (bPOI), and we show a significant correlation between downregulated GCAT1 and serum levels of follicle-stimulating hormone and anti-Müllerian hormone. Downregulation of GCAT1 inhibited G1/S cell cycle progression and thus inhibited the proliferation of GCs. Mechanistically, we show that GCAT1 competes with cyclin-dependent kinase inhibitor 1B (CDKN1B) mRNA for polypyrimidine tract-binding protein 1 (PTBP1) binding, and thus decreased GCAT1 might promote PTBP1 binding to CDKN1B mRNA and thereby initiate CDKN1B protein (p27) translation. Together, our results suggest that downregulation of GCAT1 under conditions of bPOI inhibits the proliferation of GCs through PTBP1-dependent p27 regulation, thus suggesting a novel form of lncRNA-mediated epigenetic regulation of GC function that contributes to the pathogenesis of POI. Dysfunction of granulosa cells (GCs) leading to follicle atresia has been extensively studied as a major cause of premature ovarian insufficiency (POI), but the regulatory role of long non-coding RNAs (lncRNAs) in this process is still poorly understood. Here, we show that the lncRNA LINC02690 or GCAT1 (granulosa cell-associated transcript 1) is downregulated in GCs from patients with biochemical POI (bPOI), and we show a significant correlation between downregulated GCAT1 and serum levels of follicle-stimulating hormone and anti-Müllerian hormone. Downregulation of GCAT1 inhibited G1/S cell cycle progression and thus inhibited the proliferation of GCs. Mechanistically, we show that GCAT1 competes with cyclin-dependent kinase inhibitor 1B (CDKN1B) mRNA for polypyrimidine tract-binding protein 1 (PTBP1) binding, and thus decreased GCAT1 might promote PTBP1 binding to CDKN1B mRNA and thereby initiate CDKN1B protein (p27) translation. Together, our results suggest that downregulation of GCAT1 under conditions of bPOI inhibits the proliferation of GCs through PTBP1-dependent p27 regulation, thus suggesting a novel form of lncRNA-mediated epigenetic regulation of GC function that contributes to the pathogenesis of POI.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".