miR-384-5p promotes spinal cord injury recovery in rats through suppressing of autophagy and endoplasmic reticulum stress.

BACKGROUND

Spinal cord injury (SCI) is one of the most serious neurological disorders and is characterized by high morbidity and disability. Unfortunately, there is a lack of effective treatment. Recently, the micro RNA, miR-384-5p, was reported to play a significant role in cell survival in response to different insults.

METHODS

In vitro model of traumatic neuronal injury was induced by application of a sharp sterile blade to generate cuts in PC12 cells, and in vivo SCI was produced by applying vascular clips (force of 15 g) to the dura via T9-T10 laminectomy, and then, the role of miR-384-5p in the development of SCI was investigated.

RESULTS

Dual-luciferase reporter assays confirmed that miR-384-5p regulates the gene expression of Beclin-1, an important promoter of autophagy. Quantitative polymerase chain reaction and western blot analyses revealed that treatment with miR-384-5p decreased mRNA and protein expression of Beclin-1 in the mechanically injured PC12 cells. In rats with spinal cord compression injuries, miR-384-5p expression was significantly decreased. Treatment with miR-384-5p increased spinal cord neuron survival and promoted locomotor function recovery in rats. Further study revealed that miR-384-5p administration decreased immunofluorescent labeling of Beclin-1 in spinal cord tissues and reduced autophagosome formation in neurons, as shown by transmission electron microscopy. These results indicated that miR-384-5p promotes recovery of rats with SCI by suppressing autophagy via direct targeting of Beclin-1. Moreover, miR-384-5p also inhibited the activation of endoplasmic reticulum (ER) stress by decreasing GRP78 expression in both in vitro and in vivo models.

CONCLUSIONS

This study for the first time demonstrates that the protective role of miR-384-5p in the process of SCI is associated with simultaneous suppression of autophagy and ER stress and miR-384-5p could be a promising candidate for SCI therapeutics.