Novel circular RNA 2960 contributes to secondary damage of spinal cord injury by sponging miRNA‐124

Abstract

Recent studies have shown that circular RNAs (circRNAs) are involved in many human diseases, but their roles in secondary damage after spinal cord injury (SCI) remain unclear. In the current study circRNA sequencing was performed in the damaged tissues of SCI rats on the seventh day after injury, and related molecular mechanisms were investigated. Quantitative PCR validations of molecules that exhibited significantly altered expression in SCI mice were performed. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to assess differentially expressed circRNAs. A novel circRNA-2960 was the most significantly upregulated in the SCI group. It could downregulate its target molecule miRNA-124, then exacerbate the inflammatory response and induce apoptosis at the lesion site. Disrupting circRNA-2960 expression promoted recovery of tissues affected by secondary SCI damage. The results of the present study may provide new insight into the mechanisms of secondary injury in SCI, and a new molecular marker for the diagnosis and treatment of SCI.

New Insight of Circular RNAs' Roles in Central Nervous System Post-Traumatic Injury

“…There was also a study of 7 days after SCI. Results showed that differentially expressed circRNAs related with "metabolic process, " "intracellular organelles, " "nucleic acid binding, " and "MAPK signaling pathway" (Chen et al, 2020). These results suggest that circRNAs participate in the transcription, metabolism, and other crucial biological processes in cells to regulate the process of repair after SCI.…”

“…It was proved that circRNA_2960 could aggravate the inflammatory response and induce apoptosis at the site of injury. The study further demonstrated that blocking the expression of circRNA_2960 could be beneficial to the recovery of spinal cord injured tissues (Chen et al, 2020). However, the functional relationship between miRNA-124 and mRNA remains to be explored by subsequent researches.…”

“…Contusion injury can be caused by regulating different weights and falling heights. The injured spinal cord segments were concentrated in T8-T10 in various studies (Qin et al, 2018;Zhou et al, 2019;Chen et al, 2020;Liu et al, 2020;Wang et al, 2020d;Yao et al, 2020). Two studies explored the expression of circRNAs within a short period after SCI.…”

“…Some results of TBI and SCI are similar in the existing reports on enrichment analysis of differentially expressed circRNAs. For example, circRNAs in both TBI and SCI participate in "organelle organization" (Zhao et al, 2018;Chen et al, 2020), "synapse" (Xie et al, 2018;Liu et al, 2020), and "protein binding" (Zhao et al, 2018;Liu et al, 2020) in the GO term analysis. They also participated in the "axon guidance" (Xie et al, 2018;Chen et al, 2019b in the KEGG pathways.…”

Circular RNAs: The Novel Actors in Pathophysiology of Spinal Cord Injury

“…By GO (Gen Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, dysregulation of circRNAs expression profiles have been found during the immediate, intermediate, and acute phases of secondary traumatic SCI (Qin et al, 2019 ; Zhou et al, 2019 ; Liu et al, 2020 ; Chen et al, 2021 ; Xu et al, 2021 ). Indeed, the potential function of circRNAs after acute traumatic SCI in rats were predicted by bioinformatic analysis on the three criteria (cellular components, biological process, and molecular functions), revealing the upregulated circRNAs were associated with nuclear proteins while downregulated circRNAs to proteins active in the cytoplasm (Zhou et al, 2019 ) and proposing that circRNAs may participate through different molecular mechanisms in SCI pathology.…”