The protective effect of microRNA-21 in neurons after spinal cord injury

Tao Zhang,Hongbin Lu,Ye Lang,Zixiang Luo,Jianzhong Hu,Shuangfei Ni

doi:10.1038/s41393-018-0180-1

Abstract

Study designExperimental animal study.ObjectivesTo validate the anti-apoptosis effect of microRNA-21 in neurons after spinal cord injury (SCI) and explore the mechanism.SettingXiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China.MethodsIn situ hybridization was used to detect the expression of miR-21 in spinal cord neurons (n = 24). In a rat contusion SCI model (n = 48), we upregulated the miR-21 level around the injured area using miR-21 lentiviral vectors and evaluated the therapeutic effect with histology and behavioural scores. In neuronal cells, oxygen-glucose deprivation (OGD) was exerted to imitate SCI, and we explored the biomechanism using molecular biology and a dual-luciferase reporter assay.ResultsmiR-21 was expressed in spinal cord neurons and was found to improve neuronal survival and promote functional recovery in rat SCI models. The in vitro results in PC-12 cells revealed that the augmentation of endogenous miR-21 was able to reduce neuronal cell death after OGD. In addition, overexpression of miR-21 was able to reduce cellular apoptosis via decreasing PDCD4 protein levels, and caspase-3 activity was also influenced. Transfection of miR-21 into 293T cells was able to decrease luciferase activity in a reporter assay system, including the 3′ untranslated region of PDCD4.ConclusionsmiR-21 may have a protective role in neuronal apoptosis after SCI. PDCD4 may be a functional target gene involved in the miR-21-mediated anti-apoptotic effect through an miR-21/PDCD4/caspase-3 pathway.

Highlights

To treat spinal cord injury (SCI) more effectively, many basic and clinical investigators focus on the underlying pathological mechanisms of SCI, which involve primary mechanical injury and secondary injury
We explored the potential mechanisms by examining PDCD4, which was associated with ischaemia/hypoxia reperfusion-induced apoptosis [10]
Overexpression of miR21 could decrease the apoptosis of neurons by inhibiting the PDCD4/caspase-3 pathway and improve the recovery of locomotor function

Summary

Introduction

To treat spinal cord injury (SCI) more effectively, many basic and clinical investigators focus on the underlying pathological mechanisms of SCI, which involve primary mechanical injury and secondary injury. These authors contributed : Jianzhong Hu, Hongbin Lu. miRNAs are endogenous non-coding RNAs (18–22 nucleotides) that can negatively regulate gene expression at the post-transcriptional level [3]. Several miRNAs have been detected in the mammalian brain and spinal cord, and they seem to play vital roles in some neurological functions [4, 5]. MiR-21 is a strong antiapoptotic gene in solid tumours [6] that regulates the expression of certain genes, such as PDCD4 and PTEN. The relevant biological roles of miR-21 in spinal cord neurons remain poorly understood and require further study

Methods

Results

Conclusion