Identification of Circular RNA Expression Profiles and their Implication in Spinal Cord Injury Rats at the Immediate Phase

J Mol Neurosci. 2020 Nov;70(11):1894-1905. doi: 10.1007/s12031-020-01586-9. Epub 2020 Jun 10.

Abstract

This study aimed to explore the implication of circular RNA (circRNA) expression profiles in spinal cord injury (SCI) rats at the immediate phase. CircRNA expression profiles in spinal cord samples from five SCI rats at the immediate phase (2 h post SCI) and five sham control (Ctrl) rats were assessed by microarray analysis. Subsequently, ten candidate circRNAs (obtained from microarray analysis) were validated in ten SCI rats at the immediate phase and ten Ctrl rats by the reverse transcription quantitative polymerase chain reaction (RT-qPCR). PCA plots and heatmap analyses revealed that circRNA expression profiles could distinguish SCI rats at the immediate phase from Ctrl rats. Furthermore, 1101 circRNAs were upregulated and 897 circRNAs were downregulated in SCI rats at the immediate phase compared with Ctrl rats. These dysregulated circRNAs distributed on all chromosomes, and most of them located on chromosome 1-10. As for circRNA types, most of these dysregulated circRNAs were exonic. Additionally, enrichment analyses displayed that these dysregulated circRNAs were enriched in multiple signaling pathways related to neuronal signal transduction, immunity, and inflammation, such as the calcium signaling pathway, JAK-STAT signaling pathway, and MAPK signaling pathway. Using RT-qPCR, eight out of ten candidate circRNAs (including rno_circRNA_011690, rno_circRNA_011494, rno_circRNA_005470, rno_circRNA_014301, rno_circRNA_009608, rno_circRNA_016031, rno_circRNA_011497, and rno_circRNA_015152) were dysregulated in SCI rats at the immediate phase compared with Ctrl rats. Our study provides a valuable reference for circRNA expression profiles in SCI rats at the immediate phase, which offers new clues for investigating mechanisms underlying the immediate phase and possible early intervention targets of SCI.

Keywords: Circular RNA; Expression profile; Immediate phase; Reverse transcription quantitative polymerase chain reaction; Spinal cord injury.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Chromosomes / genetics
  • Female
  • MAP Kinase Signaling System / genetics
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Spinal Cord / metabolism*
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / metabolism*
  • Up-Regulation

Substances

  • Biomarkers
  • RNA, Circular
  • STAT Transcription Factors