miR-107-5p mitigates spinal cord injury by targeting the PLOD2/HK2 axis.

Abstract

BACKGROUND: Spinal cord injury (SCI) induces persistent neuroinflammation and metabolic disturbances that contribute to neuropathic pain and neuronal damage. Although microRNAs are involved in these processes, their regulatory roles remain incompletely understood. This study aimed to identify miRNA-associated metabolic regulators linking glycolytic alterations with neuroinflammatory responses after SCI. METHODS: A contusion-induced mouse SCI model was used to assess behavioral sensitivity, motor function, and histological, molecular, and ultrastructural changes. Transcriptomic and microRNA profiling were performed to identify candidate regulators. Functional validation of miR-107-5p was conducted in BV-2 microglia and in vivo through overexpression studies, focusing on metabolic activity, microglial polarization, and cell death-related pathways. RESULTS: SCI reduced pain thresholds and motor performance and induced neuronal injury, mitochondrial abnormalities, and pro-inflammatory microglial activation. Transcriptomic analysis revealed sustained upregulation of the glycolytic regulators PLOD2 and HK2. Integrative profiling identified miR-107-5p as a potential upstream regulator of PLOD2. Overexpression of miR-107-5p in vitro and in vivo decreased PLOD2 and HK2 expression, reduced glycolytic activity, and attenuated inflammatory and apoptotic responses. These effects were diminished following PLOD2 knockdown, suggesting a PLOD2-dependent mechanism. Intrathecal administration of miR-107-5p in SCI mice was associated with higher pain thresholds, better motor performance, and reduced markers of neuroinflammation and neural injury. CONCLUSIONS: miR-107-5p modulates glycolytic metabolism and inflammatory signaling after SCI, in part through regulation of the PLOD2/HK2 pathway. These findings provide mechanistic insight into miRNA-mediated metabolic regulation in SCI and support further investigation of miR-107-5p in the context of post-injury neuroinflammation.