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

Abstract

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.