Differential expression of
non-coding RNA after traumatic
spinal cord injury (TSCI) is closely related to the pathophysiological process. The purposes of this study were to systematically profile and characterize expression of
circular RNA (
circRNA) in the lesion epicenter of spinal tissues after TSCI, and predict the structure and potential function of the regulatory
circRNA/
miRNA network. Forty-eight C57BL/6 mice were randomly and equally assigned to two groups: one subjected to TSCI at T8-10 with an Allen's drop impactor, and a second subjected to
laminectomy without TSCI. Spinal cord samples were stained with
hematoxylin and
eosin, sequenced, and validated.
RNA-Seq, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and network analyses (Targetscan and miRanda) were used to predict and annotate the
circRNA/
miRNA/
mRNA network.
Luciferase reporter, quantitative reverse transcription polymerase chain reaction, and western blot assays were used to profile expression and regulation patterns of the network in mouse models of TSCI.
Hematoxylin-
eosin staining revealed severe damage to the blood-spinal cord barrier after TSCI. Differentially expressed
circRNA and
miRNA profiles were obtained after TSCI; differentially expressed
circRNAs, which were abundant in the cytoplasm, were involved in positive regulation of transcription and
protein phosphorylation. miR-135b-5p was the most significantly downregulated
miRNA after TSCI; circRNAAbca1 and KLF4 were predicted to be its target
circRNA and
mRNA, respectively. Subsequently, the circAbca1/miR-135b-5P/KLF4 regulatory axis was predicted and constructed, and its targeted binding was verified. After inhibiting circAbca1, GAP43 expression was upregulated. Differential expression of
circRNAs might play an important role after TSCI. circAbca1 plays a neuroinhibitory role by targeted binding of the miR-135b-5P/KLF4 axis. The identified
circRNA/
miRNA/
mRNA network could provide the basis for understanding pathophysiological mechanisms underlying TSCI, as well as guide the formulation of related therapeutic strategies. All animal protocols were approved by the Research Ethics Committee of West China Hospital of China (approval No. 2017128) on May 16, 2017.