Exploration of the role of circRNAs as regulators of spinal cord injury through integrated analyses of patterns of circRNA and mRNA expression

ABSTRACT: Circular RNAs (circRNAs) exhibit diverse intracellular functions through their ability to bind to RNA, DNA, and protein structures, influencing biological processes at both transcriptional and post-transcriptional levels. To date, however, few studies have sought to profile circRNA expression in the epicentral regions of spinal lesions in the context of spinal cord injury (SCI). Accordingly, this study was designed to assess circRNA and mRNA expression profiles in this pathological setting so as to gain insight regarding the ability of circRNAs to influence SCI development and resolution. A microarray-based approach was thus used to simultaneously measure the levels of these RNAs, with qPCR, fluorescence in situ hybridization and Western immunoblotting being further used to expand on these analyses and associated regulatory mechanisms in a rat SCI model system. In total, SCI was found to be associated with the differential expression of 414 and 5337 circRNAs and mRNAs, respectively. Pathway enrichment analyses suggested that these abnormally expressed circRNAs and mRNAs were associated with key SCI-related pathways and processes, with the cytokine-cytokine receptor interaction and neuroactive ligand-receptor interaction pathways being most strongly enriched. GSEA analyses of all identified mRNAs revealed that those which were differentially expressed were primarily associated with inflammatory immune response activity. Further screening of these inflammation-associated genes was used to construct and analyze a competing endogenous RNA network. Overall, these results emphasize the critical roles that circRNAs are likely to play in the pathophysiology of SCI, highlighting multiple important genes that play regulatory roles in this setting and providing a robust foundation for further research exploring the mechanisms governing the pathogenesis and potential therapeutic targets of SCI.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE210609 | GEO | 2022/08/06

REPOSITORIES: GEO