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Spinal cord injury (SCI), one of the most severe types of neurological damage, results in persistent motor and sensory dysfunction and involves complex gene alterations. Circular RNAs (circRNAs) are a recently discovered class of regulatory molecules, and their roles in SCI still need to be addressed. This study comprehensively investigated circRNA alterations in rats across a set time course (days 0, 1, 3, 7, 14, 21, and 28) after hemisection SCI at the right T9 site. A total of 360 differentially expressed circRNAs were identified using RNA sequencing. From these, the functions of the exonic circRNA_01477 were further explored in cultured spinal cord astrocytes. Knockdown of circRNA_01477 significantly inhibited astrocyte proliferation and migration. The circRNA_01477/microRNAs (miRNA)/messenger RNA (mRNA) interaction network was visualized following microarray assay. Among the downregulated differentially expressed mRNAs, four of the seven validated genes were controlled by miRNA-423-5p. We then demonstrated that miRNA-423-5p is significantly upregulated after circRNA_01477 depletion. In summary, this study provides, for the first time, a systematic evaluation of circRNA alterations following SCI and an insight into the transcriptional regulation of the genes involved. It further reveals that circRNA_01477/miR-423-5p could be a key regulator involved in regulating the changeable regeneration environment that occurs during recovery from SCI.

Differential Circular RNA Expression Profiles Following Spinal Cord Injury in Rats: A Temporal and Experimental Analysis