Mol Neurobiol. 2025 Dec 8;63(1):268. doi: 10.1007/s12035-025-05373-8.
ABSTRACT
We previously reported the important role of miR-30d-5p in neuronal apoptosis in developing brains with hypoxia-ischemia; however, the specific mechanisms remain unclear. Here, we studied the mechanisms underlying the effects of miR-30d-5p in neonatal mice with hypoxic-ischemic brain damage (HIBD) and primary neurons exposed to oxygen-glucose deprivation (OGD). RNA-seq showed that lncRNA PVT1 was the most differentially expressed long noncoding RNAs (lncRNAs) with predicted binding sites for miR-30d-5p. FISH combined with immunofluorescence staining showed that lncRNA PVT1 was abundant in the cytoplasm of neurons and increased after HIBD or OGD. PVT1 inhibition promoted OGD-induced neuronal apoptosis and aggravated brain injury, as evidenced by increased infarct volume and impaired spatial memory. Conversely, PVT1 overexpression alleviated brain injury, as proved by ameliorative pathological changes and improved neurological deficits. Furthermore, we found that PVT1 modulated neuronal apoptosis via upregulating CaMKIIδ through sponging miR-30d-5p. PVT1 knockdown decreased CaMKIIδ expression and reduced the inhibitory phosphorylation of GSK3β, which was obviously reversed by the miR-30d-5p inhibitor. Together, these data suggest that PVT1 functions as a neuroprotective factor in brain injury induced by hypoxia-ischemia through regulating neuronal apoptosis via the PVT1/miR-30d-5p/CaMKIIδ axis .
PMID:41359209 | DOI:10.1007/s12035-025-05373-8