Integrated multi-omics profiling uncovers miRNA-guided regulatory networks after spinal cord injury in rats

Spinal cord injury (SCI) is a debilitating condition with no effective treatment. The injury triggers a complex cascade of molecular and cellular events that drive both damage and repair processes. To explore these mechanisms, we performed a comprehensive multi-omics analysis in a rat compression model of SCI, focusing on the acute phase. Transcriptomic profiling revealed extensive gene dysregulation, highlighting early inflammation, neuronal death, and synaptic dysfunction, followed by the initiation of reparative processes. Cell type composition analysis showed a rapid infiltration of peripheral immune cells; activation of microglia; and loss of neurons, astrocytes, and oligodendrocytes. Importantly, we provide experimental support for predicted microRNA (miRNA)-mRNA-protein interactions, offering a foundation for further mechanistic studies. miRNA profiling uncovered a highly dysregulated miRNA landscape, with the miR-17∼92 cluster emerging as a key regulator of neurogenesis, synaptic activity, and cell survival. Integrative miRNA-mRNA-protein analysis identified potential therapeutic targets, including miR-20a, whose inhibition <i>in vitro</i> supported neurogenesis and reduced apoptosis under oxidative stress. Our findings provide new insights into the molecular mechanisms of SCI and highlight miRNAs as potential targets for therapeutic intervention.