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Construction and analysis of a spinal cord injury competitive endogenous RNA network based on the expression data of long noncoding, micro? and messenger RNAs.

ABSTRACT: Spinal cord injury (SCI) results from trauma and predominantly affects the young male population. SCI imposes major and permanent life changes, and is associated with high future mortality and disability rates. Long non-coding RNAs (lncRNAs) have recently been demonstrated to serve critical roles in a broad range of biological processes and to be expressed in various diseases, including in SCI. However, the precise mechanisms underlying the roles of lncRNAs in SCI pathogenesis remain unexplored. In the present study, the aim was to identify critical differentially expressed lncRNAs in SCI based on the competing endogenous RNA (ceRNA) hypothesis by mining data from the Gene Expression Omnibus database of the National Center for Biotechnology Information and to unveil the functions of these lncRNAs. Different approaches and tools were employed to establish a network consisting of 13 lncRNA, 93 messenger RNA and 9 microRNA nodes, with a total of 202 edges. Three node lncRNAs were identified based on the degree distribution of the nodes, and their corresponding subnetworks were subsequently constructed. Based on these subnetworks, the biological pathways and interactions of these 3 lncRNAs were detailed using FunRich software (version 3.0). The primary results of the 3 lncRNA enrichment analyses were that they were associated with autophagy, extracellular communication and transcription factor networks, respectively. The phosphoinositide 3?kinase/protein kinase B/mammalian target of rapamycin signaling pathway of XR_350851 was the classic autophagy pathway, indicating that XR_350851 may regulate autophagy in SCI. The possible role of XR_350851 in SCI revealed in the current study based on the regulatory mechanism of ceRNAs has uncovered a new repertoire of molecular factors with potential as novel biomarkers and therapeutic targets in SCI.

SUBMITTER: Wang L

PROVIDER: S-EPMC6423625 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Construction and analysis of a spinal cord injury competitive endogenous RNA network based on the expression data of long noncoding, micro‑ and messenger RNAs.

Wang Linbang L Wang Bing B Liu Jingkun J Quan Zhengxue Z

Molecular medicine reports 20190222 4

Spinal cord injury (SCI) results from trauma and predominantly affects the young male population. SCI imposes major and permanent life changes, and is associated with high future mortality and disability rates. Long non-coding RNAs (lncRNAs) have recently been demonstrated to serve critical roles in a broad range of biological processes and to be expressed in various diseases, including in SCI. However, the precise mechanisms underlying the roles of lncRNAs in SCI pathogenesis remain unexplored. ...[more]

PMID: 30816457

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Project description:Following traumatic spinal cord injury, acute demyelination of spinal axons is followed by a period of spontaneous remyelination. However, this endogenous repair response is suboptimal and may account for the persistently compromised function of surviving axons. Spontaneous remyelination is largely mediated by Schwann cells, where demyelinated central axons, particularly in the dorsal columns, become associated with peripheral myelin. The molecular control, functional role and origin of these central remyelinating Schwann cells is currently unknown. The growth factor neuregulin-1 (Nrg1, encoded by NRG1) is a key signalling factor controlling myelination in the peripheral nervous system, via signalling through ErbB tyrosine kinase receptors. Here we examined whether Nrg1 is required for Schwann cell-mediated remyelination of central dorsal column axons and whether Nrg1 ablation influences the degree of spontaneous remyelination and functional recovery following spinal cord injury. In contused adult mice with conditional ablation of Nrg1, we found an absence of Schwann cells within the spinal cord and profound demyelination of dorsal column axons. There was no compensatory increase in oligodendrocyte remyelination. Removal of peripheral input to the spinal cord and proliferation studies demonstrated that the majority of remyelinating Schwann cells originated within the injured spinal cord. We also examined the role of specific Nrg1 isoforms, using mutant mice in which only the immunoglobulin-containing isoforms of Nrg1 (types I and II) were conditionally ablated, leaving the type III Nrg1 intact. We found that the immunoglobulin Nrg1 isoforms were dispensable for Schwann cell-mediated remyelination of central axons after spinal cord injury. When functional effects were examined, both global Nrg1 and immunoglobulin-specific Nrg1 mutants demonstrated reduced spontaneous locomotor recovery compared to injured controls, although global Nrg1 mutants were more impaired in tests requiring co-ordination, balance and proprioception. Furthermore, electrophysiological assessments revealed severely impaired axonal conduction in the dorsal columns of global Nrg1 mutants (where Schwann cell-mediated remyelination is prevented), but not immunoglobulin-specific mutants (where Schwann cell-mediated remyelination remains intact), providing robust evidence that the profound demyelinating phenotype observed in the dorsal columns of Nrg1 mutant mice is related to conduction failure. Our data provide novel mechanistic insight into endogenous regenerative processes after spinal cord injury, demonstrating that Nrg1 signalling regulates central axon remyelination and functional repair and drives the trans-differentiation of central precursor cells into peripheral nervous system-like Schwann cells that remyelinate spinal axons after injury. Manipulation of the Nrg1 system could therefore be exploited to enhance spontaneous repair after spinal cord injury and other central nervous system disorders with a demyelinating pathology.media-1vid110.1093/brain/aww039_video_abstractaww039_video_abstract.

Dataset Information

Construction and analysis of a spinal cord injury competitive endogenous RNA network based on the expression data of long noncoding, micro? and messenger RNAs.

Publications

Construction and analysis of a spinal cord injury competitive endogenous RNA network based on the expression data of long noncoding, micro‑ and messenger RNAs.

Similar Datasets

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