RNA-Seq analysis of coding and long non-coding RNAs in the sub-chronic and chronic stages of spinal cord injury

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE93249 | GEO | 2017/01/07

SECONDARY ACCESSION(S): PRJNA360420

REPOSITORIES: GEO