LncRNA H19 Regulates Lipopolysaccharide (LPS)-Induced Apoptosis and Inflammation of BV2 Microglia Cells Through Targeting miR-325-3p/NEUROD4 Axis.

Spinal cord injury (SCI) is a devastating traumatic event worldwide. Work from the past decade has highlighted the key involvement of long non-coding RNAs (lncRNAs) in SCI. Nevertheless, the molecular action of lncRNA H19 in SCI is still not fully understood. The levels of H19, microRNA (miR)-325-3p, and neuronal differentiation 4 (NEUROD4) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Flow cytometry was performed to assess cell apoptosis. The levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and IL-6 were detected using the enzyme-linked immunosorbent assay (ELISA). Targeted relationships among H19, miR-325-3p, and NEUROD4 were confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP), or RNA pull-down assays. Our data showed that H19 level was overexpressed in lipopolysaccharide (LPS)-treated BV2 cells. H19 silencing alleviated LPS-evoked cell apoptosis and inflammation. Mechanistically, H19 in BV2 cells directly targeted miR-325-3p, and NEUROD4 was a direct target of miR-325-3p. Moreover, miR-325-3p was a functional target of H19 in regulating cell apoptosis and inflammation induced by LPS. Enforced expression of miR-325-3p relieved LPS-evoked cell apoptosis and inflammation through reducing NEUROD4. Furthermore, H19 in BV2 cells regulated NEUROD4 expression through targeting miR-325-3p. Our results identified that the silencing of H19 attenuated LPS-evoked microglia cell apoptosis and inflammation after SCI at least partially through targeting the miR-325-3p/NEUROD4 axis, highlighting a novel approach for SCI management.