Dysregulated circRNA expression profile and associated miRNA sponging in abnormal lung development in congenital diaphragmatic hernia
Bibliographic record
Abstract
RATIONALE: Circular RNAs (circRNAs) are stable, tissue- and developmental-stage-specific regulators of gene expression and candidate disease biomarkers. Their expression profile in abnormal lung development in congenital diaphragmatic hernia (CDH) is unknown. OBJECTIVE: To evaluate circRNA expression profile in CDH-associated abnormal lung development. METHODS: We profiled circRNAs in rat CDH and control lungs at embryonic day (E)15 and E21 by microarray. We validated identified circRNAs using back‒splice junction amplicon sequencing, RT-qPCR and in situ hybridisation. We modified a circRNA function prediction tool to predict circRNA::micro(mi)RNA::messenger(m)RNA interactions and compared these with Oxford Nanopore RNA sequencing and existing human CDH datasets. MEASUREMENTS AND MAIN RESULTS: Microarrays revealed a unique circRNA biosignature during CDH lung development. CircAnp32e was expressed in a sex-specific and spatiotemporal expression pattern in the epithelium at E15. The predicted mature sequence of circAnp32e overlapped 90% with its human orthologue. circRNA::miRNA::mRNA interaction networks at E15 and E21 revealed enrichment in inflammation/infection, smooth muscle cell function, cell proliferation/cell cycle regulation and response to hypoxia pathways. Parental genes of differentially expressed circRNAs at E15 enriched pathways linked to cell proliferation/cell cycle/cancer, while at end-gestation, inflammation and cardiovascular processes were also overrepresented. Rat and human CDH lungs showed overlapping pathways with additional enrichment for RNA processing and protein binding/modification in humans. In a human bronchial epithelial (BEAS-2B) nitrofen-injury model, ANP32E and circANP32E were downregulated, and the predicted let-7 target was significantly dysregulated. CONCLUSION: A unique circRNA signature during abnormal lung development in CDH may mediate inflammatory responses, smooth muscle cell function and cell proliferation regulation via miRNA sponging. Overlap of downstream pathways in rat and human CDH suggests conserved functions across species. This circRNA biosignature defines strong candidate biomarkers for CDH and a basis for future prospective prenatal investigation.
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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 | 0.000 |
| 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".