EVADR lncRNA Mitigates Neonatal Hypoxic-Ischemic Brain Injury via the miR-145→WNT/β-Catenin Axis and Exhibits Biomarker Potential.

Perinatal hypoxic-ischemic injury (HI) upregulated an endogenous retrovirus-derived lncRNA, EVADR, via HIF-1α/NF-κB. EVADR bound and repressed miR-145, thereby activating WNT/β-catenin signaling. Binding specificity was confirmed by biotin-miRNA pull-down and mutant-seed luciferase reporters. Genetic (si-CTNNB1/si-WNT3A) and pharmacologic (XAV939/CHIR99021) cross-validation demonstrated pathway necessity and rescue. EVADR gain-of-function reduced neuronal death and inflammation and improved behavioral outcomes following HI. Circulating EVADR levels in plasma/CSF correlated with injury severity; ROC analyses indicated diagnostic potential alone and combined with S100B/NSE. These data support EVADR-miR-145→WNT/β-catenin as a mechanistic axis with translational relevance.