The Molecular Mechanism of LncRNA LUCAT1 Regulating HSPB8 Expression via miR-337-3p in Modulating Neurological Damage After Cerebral Infarction.

This study aims to investigate the role of the lncRNA LUCAT1 in cerebral infarction-induced neurological damage. In vitro experiments employed N2a cells to establish an OGD/R model, while in vivo experiments utilized male C57BL/6 mice to construct a MCAO model. Cell viability and apoptosis were assessed via the CCK-8 assay and flow cytometry, respectively. RT-qPCR measured mRNA expression of LUCAT1, miR-337-3p, and HSPB8. The molecular targeting relationship was validated using dual luciferase reporter assays and RNA pull-down experiments. ELISA was used to measure the levels of IL-6, IL-1β, and TNF-α. DCFH-DA fluorescent probes and commercial kits were employed to measure ROS levels, MDA and SOD activity. Neurological function assessment included Longa score, Bederson score, adhesive removal test, and modified neurological severity score. In both OGD/R and MCAO models, LUCAT1 expression was downregulated while miR-337-3p expression was upregulated. LUCAT1 was found to directly bind to miR-337-3p. Under OGD/R conditions, LUCAT1 overexpression enhanced cell viability, inhibited apoptosis, and alleviated inflammation and oxidative stress, with these protective effects being reversed by miR-337-3p overexpression. Animal experiments further confirmed that LUCAT1 overexpression improved neuroinflammation, oxidative stress, and neurological deficits in MCAO mice, an effect that was attenuated by co-expression of miR-337-3p. HSPB8 was identified as a direct target gene of miR-337-3p; inhibition of miR-337-3p exerted protective effects by upregulating HSPB8, whereas HSPB8 knockdown counteracted this protective effect. The long noncoding RNA LUCAT1 exerts neuroprotective effects in cerebral infarction by sponging miR-337-3p and relieving its inhibitory action on HSPB8.