LncRNA SNHG14 drives alveolar inflammation in bronchopulmonary dysplasia via DNMT3a-mediated epigenetic silencing of miR-214-3p.

OBJECTIVE AND

DESIGN

This experimental study investigated whether lncRNA SNHG14 contributes to hyperoxia-associated bronchopulmonary dysplasia (BPD) through DNMT3a-mediated epigenetic regulation of miR-214-3p and evaluated TfR-modified exosome-mimetic nanovesicles as an siRNA delivery platform.

MATERIAL OR SUBJECTS: Hyperoxia-exposed murine alveolar epithelial type II cells and neonatal C57BL/6J mice were used.

TREATMENT: Cells and neonatal mice were exposed to 85% O2 or normoxia. In vivo groups included normoxia, BPD, BPD + blank EMNVs, BPD + free siSNHG14, BPD + TfR-EMNVs-siSNHG14, and BPD + TfR-EMNVs-siSNHG14 + miR-214-3p antagomir.

METHODS

Transcriptomic, miRNA, methylation, pull-down, RIP, ChIP-qPCR, luciferase, biodistribution, histological, biochemical, and exploratory innate immune assays were performed.

RESULTS

SNHG14 was upregulated after hyperoxia. SNHG14 silencing reduced epithelial injury, apoptosis, inflammation, and EMT-related changes, and was associated with decreased DNMT3a enrichment and methylation at the examined miR-214-3p promoter region. TfR-EMNVs-siSNHG14 improved siRNA delivery and lung-preferential fluorescence accumulation without overt short-term liver, kidney, or interferon-response toxicity.

CONCLUSIONS

The SNHG14/DNMT3a/miR-214-3p axis may contribute to experimental BPD-like alveolar injury, and TfR-EMNVs-siSNHG14 warrants further pharmacokinetic, safety, and clinical-sample validation.