Upregulation of miR-502-5p in traumatic spinal cord injury modulates neuroinflammation and oxidative stress by targeting FBXO28

创伤性脊髓损伤中 miR-502-5p 的上调通过靶向 FBXO28 调节神经炎症和氧化应激

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Abstract

BACKGROUND: Spinal cord injury (SCI) is a serious condition affecting the central nervous system, often caused by trauma, which can lead to lasting impairment in nerve function. OBJECTIVE: This study aims to explore the functional role of miR-502-5p in traumatic SCI, offering insights into potential therapeutic interventions. METHODS: Serum miR-502-5p levels were quantified through RT-qPCR in a clinical cohort comprising 60 controls, 50 incomplete SCI, and 30 complete SCI patients. The diagnostic potential of miR-502-5p was assessed by the ROC curve. An in vitro cellular model was established by subjecting SH-SY5Y cells to oxygen and glucose deprivation (OGD). This model was utilized to investigate cell viability, apoptosis, as well as markers of inflammation and oxidative stress. Further investigation was conducted into the downstream molecular mechanisms by which miR-502-5p affects SH-SY5Y cells. RESULTS: Serum miR-502-5p levels were elevated in individuals with SCI, with higher expression observed in cases of complete SCI compared to incomplete SCI, indicating its potential for severity assessment. Both upregulation and downregulation of miR-502-5p were found to respectively promote and attenuate OGD-induced cell apoptosis, inflammatory responses, and oxidative stress. Furthermore, F-box protein 28 (FBXO28) was validated as a direct target of miR-502-5p. Functional experiments showed that knockdown of FBXO28 counteracted the protective effects of miR-502-5p inhibition. CONCLUSIONS: MiR-502-5p shows promise as a biomarker for SCI, with its expression closely associated with injury severity. Mechanistically, it appears to facilitate the progression of SCI by directly targeting FBXO28, thereby exacerbating neuronal apoptosis, inflammatory responses, and oxidative stress.

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