Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis.

Jun Zhou,Chengxiang Yang,Qingming Xiong,Youling Fan,Hongtao Chen

doi:10.3389/fnmol.2017.00091

Abstract

Neuropathic pain (NP) is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. However, the molecular mechanisms are not fully understood. A non-coding Ribose Nucleic Acid (ncRNA) is an RNA molecule that is not translated into a protein. NcRNAs are involved in many cellular processes, and mutations or imbalances of the repertoire within the body can cause a variety of diseases. Although ncRNAs have recently been shown to play a role in NP pathogenesis, the specific effects of ncRNAs in NP remain largely unknown. In this study, sequencing analysis was performed to investigated the expression patterns of ncRNAs in the spinal cord following spared nerve injury-induced NP. A total of 134 long non-coding RNAs (lncRNAs), 12 microRNAs (miRNAs), 188 circular RNAs (circRNAs) and 1066 mRNAs were significantly regulated at 14 days after spared nerve injury (SNI) surgery. Next, quantitative real-time polymerase chain reaction (PCR) was performed to validate the expression of selected lncRNAs, miRNAs, circRNAs, and mRNAs. Bioinformatics tools and databases were employed to explore the potential ncRNA functions and relationships. Our data showed that the most significantly involved pathways in SNI pathogenesis were ribosome, PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, amoebiasis and protein digestion and absorption. In addition, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA network of NP was constructed. This is the first study to comprehensively identify regulated ncRNAs of the spinal cord and to demonstrate the involvement of different ncRNA expression patterns in the spinal cord of NP pathogenesis by sequence analysis. This information will enable further research on the pathogenesis of NP and facilitate the development of novel NP therapeutics targeting ncRNAs.

Highlights

Neuropathic pain (NP) is one type of chronic pain and is caused by primary damage and dysfunction of the nervous system, which is characterized by dysesthesia, hyperalgesia, and allodynia (Gaskin and Richard, 2012; Finnerup et al, 2016)
We determined that some non-coding Ribose Nucleic Acid (ncRNA) and mRNA.LncRNAs regulated the expression of target gene (mRNA) were induced significant changes in the spinal cord in response to spared nerve injury (SNI)-induced NP
The regulatory networks of ncRNA and mRNA were constructed. These findings prompted the proposal that ncRNAs played a significant role in NP processing, and sequencing analysis revealed a potential therapeutic target of NP

Summary

Introduction

Neuropathic pain (NP) is one type of chronic pain and is caused by primary damage and dysfunction of the nervous system, which is characterized by dysesthesia, hyperalgesia, and allodynia (Gaskin and Richard, 2012; Finnerup et al, 2016). Non-coding Ribose Nucleic Acids (ncRNAs) comprise a class of RNA molecules that typically do not encode proteins but functionally regulate protein expression (Mattick and Makunin, 2006) Based on their size, ncRNAs can be subdivided into small ncRNAs (200 bp, as well as circular RNAs (circRNA) consisting of a closed continuous loop (Thum, 2014; Thum and Condorelli, 2015). Emerging data have shown that ncRNAs are of crucial importance in various types of pain, NP (Chen et al, 2014; Shao et al, 2015; Zhang and Banerjee, 2015; Wang et al, 2016). A comprehensive forecasting and analysis of the ncRNAs underlying the progression of NP are essential for the development of effective strategies to treat this troublesome disorder and to prevent its progression

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