Altered long noncoding RNA expressions in dorsal root ganglion after rat sciatic nerve injury

Dorsal root ganglia (DRG) neurons spontaneously undergo robust neurite growth after axotomy. Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. However, the functions of lncRNAs in the regulation of responses of DRG neurons to injury stimuli remain untested. Here, lncRNA microarray analysis was performed to profile the lncRNAs in L4-L6 DRGs following rat sciatic nerve resection. The 105 lncRNAs were identified to be differentially expressed at 0, 1, 4, 7 d post injury. A coexpression network of 24 down-regulated lncRNAs and coding genes was constructed, and 115 targets of these 24 lncRNAs were found to be mainly involved in cell phenotype modulation, including glial cell migration, purinergic nucleotide receptor signaling pathway, vasodilation, regulation of multi-organism process, and neuropeptide signaling pathway, and also to be potentially associated with several key regeneration signaling pathways, including MAPK signaling pathway, and neuroactive ligand-receptor interaction. LncRNA BC089918 was selected from 24 down-regulated lncRNAs for validation by quantitative real-time polymerase chain reaction and in situ hybridization. And silencing of BC089918 with small interfering RNAs indicted that the lncRNA had a particular promoting effect on neurite outgrowth. Our data demonstrated a distinct involvement of lncRNAs in DRGs after nerve injury, thus contributing to illustration of molecular mechanisms responsible for nerve regeneration.

[1]  Shuli Kang,et al.  Large-scale prediction of long non-coding RNA functions in a coding–non-coding gene co-expression network , 2011, Nucleic acids research.

[2]  M. Bastiani,et al.  Axon Regeneration Requires a Conserved MAP Kinase Pathway , 2009, Science.

[3]  Xiaosong Gu,et al.  Construction of tissue engineered nerve grafts and their application in peripheral nerve regeneration , 2011, Progress in Neurobiology.

[4]  Xavier Navarro,et al.  Specificity of peripheral nerve regeneration: Interactions at the axon level , 2012, Progress in Neurobiology.

[5]  Guohui Ding,et al.  Profile of MicroRNAs following Rat Sciatic Nerve Injury by Deep Sequencing: Implication for Mechanisms of Nerve Regeneration , 2011, PloS one.

[6]  Howard Y. Chang,et al.  Long noncoding RNAs and human disease. , 2011, Trends in cell biology.

[7]  A. Lloyd,et al.  EphB Signaling Directs Peripheral Nerve Regeneration through Sox2-Dependent Schwann Cell Sorting , 2010, Cell.

[8]  Carlos Prieto,et al.  Human Gene Coexpression Landscape: Confident Network Derived from Tissue Transcriptomic Profiles , 2008, PloS one.

[9]  F. Costa,et al.  Non‐coding RNAs: Meet thy masters , 2010, BioEssays : news and reviews in molecular, cellular and developmental biology.

[10]  Kai-Fenp Liu,et al.  Neuronal intrinsic mechanisms of axon regeneration. , 2011, Annual review of neuroscience.

[11]  Rory Johnson Long non-coding RNAs in Huntington's disease neurodegeneration , 2012, Neurobiology of Disease.

[12]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[13]  J. Mattick,et al.  Long non-coding RNAs in nervous system function and disease , 2010, Brain Research.

[14]  Songlin Zhou,et al.  Early changes of microRNAs expression in the dorsal root ganglia following rat sciatic nerve transection , 2011, Neuroscience Letters.

[15]  Richard Simon,et al.  A random variance model for detection of differential gene expression in small microarray experiments , 2003, Bioinform..

[16]  J. Mattick,et al.  Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. , 2005, Genome research.

[17]  S. Clemens,et al.  Dicer-microRNA pathway is critical for peripheral nerve regeneration and functional recovery in vivo and regenerative axonogenesis in vitro , 2012, Experimental Neurology.

[18]  D. Spector,et al.  Long noncoding RNAs: functional surprises from the RNA world. , 2009, Genes & development.

[19]  Minna Männikkö,et al.  Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1. , 2010, Brain : a journal of neurology.

[20]  J. Mattick A new paradigm for developmental biology , 2007, Journal of Experimental Biology.

[21]  A. Tedeschi,et al.  Tuning the Orchestra: Transcriptional Pathways Controlling Axon Regeneration , 2012, Front. Mol. Neurosci..

[22]  K. Christie,et al.  PTEN Inhibition to Facilitate Intrinsic Regenerative Outgrowth of Adult Peripheral Axons , 2010, The Journal of Neuroscience.

[23]  C. Wahlestedt,et al.  Noncoding RNAs: couplers of analog and digital information in nervous system function? , 2007, Trends in Neurosciences.

[24]  F. Pauler,et al.  An RNA-Seq Strategy to Detect the Complete Coding and Non-Coding Transcriptome Including Full-Length Imprinted Macro ncRNAs , 2011, PloS one.

[25]  Xiao-Ming Xu,et al.  Altered microRNA expression following traumatic spinal cord injury , 2009, Experimental Neurology.

[26]  Paola Sebastiani,et al.  Cluster analysis of gene expression dynamics , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[27]  C. Ponting,et al.  Genomic and Transcriptional Co-Localization of Protein-Coding and Long Non-Coding RNA Pairs in the Developing Brain , 2009, PLoS genetics.