Abstract
Spinal cord injury (SCI) is mostly caused by trauma. As primary mechanical injury is unavoidable in SCI, a focus on the pathophysiology and underlying molecular mechanisms of SCI-induced secondary injury is necessary to develop promising treatments for SCI patients. Circular RNAs (circRNAs) are associated with various diseases. Nevertheless, studies to date have not yet determined the functional roles of circRNAs in traumatic SCI. We examined circRNA expression profiles in the contused spinal cords of rats using microarray and quantitative reverse transcription-PCR (qRT-PCR) then predict their potential roles in post-SCI pathophysiology with bioinformatics. We found a total of 1676 differentially expressed circRNAs (fold change ≥ 2.0; P < 0.05) in spinal cord 3 days after contusion using circRNA microarray; 1261 circRNAs were significantly downregulated, whereas the remaining 415 were significantly upregulated. Then, five selected circRNAs, namely, rno_circRNA_005342, rno_circRNA_015513, rno_circRNA_002948, rno_circRNA_006096, and rno_circRNA_013017 were all significantly downregulated in the SCI group after verification by qRT-PCR, demonstrating a similar expression pattern in both microarray and PCR data. The next section of the study was concerned with the prediction of circRNA/miRNA/mRNA interactions using bioinformatics analysis. In the final part of the study, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses indicated carbohydrate metabolic process was one of the most significant enrichments and meaningful terms after GO analysis, and the top two signaling pathways affected by the circRNAs-miRNAs axes were the AMP-activated protein kinase signaling pathway and the peroxisome related pathway. In summary, this study showed an altered circRNA expression pattern that may be involved in physiological and pathological processes in rats after traumatic SCI, providing deep insights into numerous possibilities for SCI treatment targets by regulating circRNAs.
Highlights
Spinal cord injury is a growing public health concern worldwide that is accompanied by permanent neurological impairment and attendant social and economic losses (Yang et al, 2014; Manohar et al, 2017)
We found that an array of circRNAs were differentially expressed in the early stage after spinal cord injury (SCI) based on circRNA microarray detection
Using bioinformatics tools, circRNA/miRNA/mRNA interactions were constructed according to competing endogenous RNAs (ceRNAs) mechanisms, indicating a close relationship between circRNAs, miRNAs, and their target mRNAs
Summary
Spinal cord injury is a growing public health concern worldwide that is accompanied by permanent neurological impairment and attendant social and economic losses (Yang et al, 2014; Manohar et al, 2017). SCI is mostly caused by trauma (Fan et al, 2017), which involves primary mechanical injury due to rapid direct compression and contusion on the cord and secondary injury, such as hemorrhage, edema, ischemia, cell death and oxidative stress, during the following hours (Zhu et al, 2017b). It is well-known that primary mechanical injury is hardly avoidable. As a result, concentrating on the pathophysiology and underlying molecular mechanisms of SCI-induced secondary injury is necessary to develop promising diagnosis and treatment approaches for SCI patients (Liu et al, 2017a). Past decades have seen the rapid development of stem cell transplantation (Nagoshi and Okano, 2017), surgical decompression (Yang et al, 2013; Hu et al, 2015) and high-dose methylprednisolone (Hextrum and Bennett, 2018) in the field of SCI, a multitude of controversies on the efficacy of these approaches remains
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
