Long Non-coding RNA MSTRG.24008.1 Regulates the Regeneration of the Sciatic Nerve via the miR-331-3p-NLRP3/MAL Axis.

Gang Yin,Ying Peng,Peilin Wang,Yaofa Lin,Zhuoxuan Li,Haodong Lin,Renyuan Wang

doi:10.3389/fcell.2021.641603

Abstract

Peripheral nerve injury (PNI) is a common clinical problem, which can cause severe disability and dramatically affect a patient’s quality of life. Neural regeneration after PNI is a complex biological process that involves a variety of signaling pathways and genes. Emerging studies demonstrated that long non-coding RNAs (lncRNAs) were abnormally expressed after PNI and played pivotal roles in peripheral nerve regeneration. Based on the rat sciatic nerve injury model, we found that the expression levels of several lncRNAs were increased significantly in the sciatic nerve after injury. Software prediction prompted us to focus on one up-regulated lncRNA, MSTRG.24008.1. Dual-luciferase reporter assay, RNA pull-down assay and RNA interference approach verified that MSTRG.24008.1 regulated neuroregeneration via the miR-331-3p/nucleotide-binding oligomerization domain-like pyrin domain containing 3 (NLRP3)/myelin and lymphocyte protein (MAL) axis in vitro. Subsequently, we performed gastrocnemius muscle gravity and sciatic functional index experiments to evaluate the recovery of injured sciatic nerves after MSTRG.24008.1 siRNA interference in vivo. In conclusion, knockdown of MSTRG.24008.1 promotes the regeneration of the sciatic nerve via the miR-331-3p/NLRP3/MAL axis, which may provide a new strategy to evaluate and repair injured peripheral nerves clinically.

Highlights

Peripheral nerve injury (PNI) is a common clinical problem that is mostly caused by trauma and medical disorders, resulting in a financial burden to healthcare systems (Grinsell and Keating, 2014)
The results showed that compared with the sham operation group, 27 injury-related long non-coding RNAs (lncRNAs) were upregulated and 13 injury-related lncRNAs were downregulated in the SNI group (Table 1 and Supplementary Figure 1)
The results showed that compared with those in the sham operation group, the expression levels of MSTRG.22293.1, MSTRG.24008.1, and MSTRG.4223.1 were significantly increased and the expression lncRNA MSTRG.24008.1 Promote Neural Recovery levels of MSTRG.13284.1 and MSTRG.32389.2 were significantly decreased (Figure 1D) in the SNI group, which was consistent with the RNA-seq results

Summary

Introduction

Peripheral nerve injury (PNI) is a common clinical problem that is mostly caused by trauma and medical disorders, resulting in a financial burden to healthcare systems (Grinsell and Keating, 2014). Because of the slow regeneration speed and other factors, such as the severity and site of the nerve injury, the lncRNA MSTRG.24008.1 Promote Neural Recovery regeneration distance, axonal excitability, and the inflammatory milieu, it takes a long time for axons to regenerate and reach the target organ. Further exploration of the biological process of neuroregeneration may provide new therapeutic targets. The dedifferentiated Schwann cells proliferate and migrate to the lesion to clear myelin and axon debris, form Bungner bands, and excrete neurotrophic factors, and provide a suitable microenvironment for neuroregeneration (Glenn and Talbot, 2013; Wu and Murashov, 2013). A previous study showed that large numbers of long noncoding RNAs (lncRNAs) were involved in this biological process (Yao and Yu, 2019)

Methods

Results

Conclusion