Downregulation of miR-6721-5p in the serum of patients with spinal cord injury and its role in regulating microglial inflammation via targeting RTN3.

Abstract

Spinal cord injury (SCI) remains a devastating neurological condition for which treatments are scarce. This work sought to investigate the role of miR-6721-5p in acute traumatic SCI and clarify its downstream mechanisms. Serum miR-6721-5p was measured in 122 SCI patients and 110 trauma controls, and its diagnostic value was assessed by logistic regression and ROC analysis. In cellular experiments, BV-2 microglial cells were stimulated with LPS to assess the effects of miR-6721-5p on cell viability, inflammation, and oxidative stress. The interaction between miR-6721-5p and RTN3 was validated through luciferase reporter, RNA immunoprecipitation, and rescue experiments. Compared with the control group, patients with SCI showed markedly lower levels of miR-6721-5p. This miRNA correlated negatively with injury severity, CRP, WBC, and NLR. According to the ROC curve, it had a fair ability to discriminate SCI (AUC = 0.887). Multivariate regression analysis identified miR-6721-5p as an independent protective factor. Experiments confirmed RTN3 as a direct target of miR-6721-5p. RTN3 mRNA expression was elevated in SCI patients and inversely correlated with miR-6721-5p levels. In LPS-stimulated BV-2 cells, miR-6721-5p overexpression reversed cell viability reduction and suppressed inflammation and oxidative stress, effects that were reversed by RTN3 overexpression. In patients with SCI, miR-6721-5p is markedly downregulated and may exert protective effects by targeting RTN3 to modulate microglial inflammation and oxidative stress. Results imply that miR-6721-5p holds potential as a biomarker for SCI severity, but further validation in prospective cohorts with matched trauma severity is required.