Dataset Information

Long non-coding RNAs in the spinal cord injury: Novel spotlight.

ABSTRACT: Spinal cord injury (SCI) may lead to persistent locomotor dysfunction and somatosensory disorders, which adversely affect the quality of life of patients and cause a significant economic burden to the society. The efficacies of current therapeutic interventions are still far from satisfaction as the secondary damages resulting from the complex and progressive molecular alterations after SCI are not properly addressed. Recent studies revealed that long non-coding RNAs (lncRNAs) are abundant in the brain and might play critical roles in several nervous system disorders. At the cellular level, lncRNAs have been shown to regulate the expression of protein-coding RNAs and hence participate in neuronal death, demyelination and glia activation. Notably, SCI is characterized by these biological processes, suggesting that lncRNAs could be novel modulators in the pathogenesis of SCI. This review describes recent progresses in the lncRNA transcriptome analyses and their molecular functions in regulating SCI progression.

SUBMITTER: Li Z

PROVIDER: S-EPMC6653026 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Long non-coding RNAs in the spinal cord injury: Novel spotlight.

Li Zheng Z Ho Idy H T IHT Li Xingye X Xu Derong D Wu William K K WKK Wu William K K WKK Chan Matthew T V MTV Li Shugang S Liu Xiaodong X

Journal of cellular and molecular medicine 20190529 8

Spinal cord injury (SCI) may lead to persistent locomotor dysfunction and somatosensory disorders, which adversely affect the quality of life of patients and cause a significant economic burden to the society. The efficacies of current therapeutic interventions are still far from satisfaction as the secondary damages resulting from the complex and progressive molecular alterations after SCI are not properly addressed. Recent studies revealed that long non-coding RNAs (lncRNAs) are abundant in th ...[more]

PMID: 31140726

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Project description:Background: Chronic spinal cord injury (SCI) remains one of the most debilitating neurological disorders and the majority of SCI patients are in the chronic phase. Previous studies of SCI that were limited by resources and technology have usually focused on few genes and pathways at a time. Thus, a comprehensive view of the complex molecular changes underlying SCI pathophysiology is needed. In particular, the biological roles of long non-coding RNAs (lncRNAs), a class of regulatory RNAs, have never been characterized systemically in SCI. Results: This study is the first to investigate alterations in the expression of both coding and long non-coding genes in the sub-chronic and chronic stages of SCI using RNA-Sequencing. Our data revealed differentially expressed genes, canonical pathways, and networks unique to particular time points or common to multiple time points in the progression of SCI. For example, a network of multiple critical genes responsible for astrogliosis and fibrosis was identified among differentially expressed genes common to three time points (1month, 3months, and 6 months after SCI). Moreover, the potential functions of rat lncRNAs in SCI were extensively analyzed. First, a comprehensive annotation database was compiled for rat lncRNAs that revealed several interesting characteristics of lncRNAs in the rat genome. Then, by correlating the temporal expression patterns of lncRNAs with those of protein-coding genes, we identified lncRNAs that are associated with functional categories such as signaling pathways, immune response, epigenetic modification, nervous system, and extracellular matrix. The expression patterns of some lncRNAs are highly correlated with those of their most proximal protein-coding genes, so it is possible that these lncRNAs regulate the expression of their protein-coding neighbors. Finally, we searched for transcription factor motifs enriched in the upstream regulatory regions of differentially expressed lncRNAs, and identified differentially expressed lncRNAs that are homologous to human genomic regions harboring molecular variants associated with human neurological diseases. Conclusions: Overall, our study provides an unprecedented resource for the study of sub-chronic and chronic SCI that will help the research community identify new molecular targets for future functional investigation.

Project description:Spinal cord injury (SCI) is a serious disorder of the central nervous system with a high disability rate. Long noncoding RNAs (lncRNAs) are reported to mediate many biological processes. The aim of this study was to explore lncRNA and mRNA expression profiles and functional networks after SCI. Differentially expressed genes between SCI model rats and sham controls were identified by microarray assays and analyzed by functional enrichment. Key lncRNAs were identified using a support vector machine- (SVM-) recursive feature elimination (RFE) algorithm. A trans and cis regulation model was used to analyze the regulatory relationships between lncRNAs and their targets. An lncRNA-related ceRNA network was established. We identified 5465 differentially expressed lncRNAs (DE lncRNAs) and 8366 differentially expressed mRNAs (DE mRNAs) in the SCI group compared with the sham group (fold change > 2.0, p < 0.05). Four genes were confirmed by qRT-PCR which were consistent with the microarray data. GSEA analysis showed that most marked changes occurred in pathways related to immune inflammation and nerve cell function, including cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and GABAergic synapse. Enrichment analysis identified 30 signaling pathways, including those associated with immune inflammation response. A total of 40 key lncRNAs were identified using the SVM-RFE algorithm. A key lncRNA-mRNAs coexpression network was generated for 230 951 lncRNA-mRNA pairs with half showing positive correlations. Several key DE lncRNAs were predicted to have "cis"- or "trans"-regulated target genes. The transcription factors, Sp1, JUN, and SOX10, may regulate the interaction between XR_001837123.1 and ETS 1. In addition, five pairs of ceRNA regulatory sequences were constructed. Many mRNAs and lncRNAs were found to be dysregulated after SCI. Bioinformatic analysis showed that DE lncRNAs may play crucial roles in SCI. It is anticipated that these findings will provide new insights into the underlying mechanisms and potential therapeutic targets for SCI.

Dataset Information

Long non-coding RNAs in the spinal cord injury: Novel spotlight.

Publications

Long non-coding RNAs in the spinal cord injury: Novel spotlight.

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