MicroRNA-211-5p attenuates spinal cord injury via targeting of activating transcription factor 6.

ABSTRACT

The recovery of spinal cord injury (SCI) involves multiple factors, of which miRNAs take an important part. In this study, we evaluated the function of microRNA-211-5p (miR-211-5p) on SCI in a rat model. SCI model was established using modified Allen's weight-drop method and Basso-Bcattie-Bresnahan score was applied to assess the locomotor function. MiR-211-5p agomir was utilized to increase miR-211-5p expression and endoplasmic reticulum (ER) stress inhibitor, 4-PBA (4-phenylbutyric acid), was utilized to suppress ER stress. Neuron apoptosis and the expressions of miR-211-5p, activating transcription factor 6 (ATF6), apoptosis-related proteins, pro-inflammatory cytokines and endoplasmic reticulum stress-related proteins were detected. Dual luciferase reporter gene assay was performed to verify the binding between miR-211-5p and ATF6. The results showed that miR-211-5p directly targeted ATF6. MiR-211-5p was down-regulated and ATF6 was up-regulated in SCI rats. Both interferences with miR-211-5p agomir and 4-PBA effectively attenuated neuron apoptosis and reversed the expressions of apoptosis, inflammation and endoplasmic reticulum stress-related molecules post SCI in rats. These findings demonstrated that miR-211-5p could effectively alleviate SCI-induced neuron apoptosis and inflammation via directly targeting ATF-6 and regulating ER stress.