Abstract
BackgroundSpinal cord ischemia/reperfusion injury (SCII) is a catastrophic complication involved with cardiovascular, spine, and thoracic surgeries and can lead to paraplegia. Nevertheless, the molecular mechanism of SCII remain ill-defined.MethodsExpression profiling (GSE138966) data were obtained from GEO database. Then, differentially expressed (DE) lncRNAs and DEmRNAs were screened out with p < 0.05, and | fold change| > 1.5. Aberrant miRNAs expression in SCII was obtained from PubMed. Functional enrichment analysis of overlapping DEmRNAs between predicted mRNAs in miRDB database and DEmRNAs obtained from GSE138966 was performed using cluster Profiler R package. The lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network was established in light of ceRNA theory. The key lncRNAs in the ceRNA network were identified by topological analysis. Subsequently, key lncRNAs related ceRNA-pathway network and transcription factors (TFs)-mRNAs network were constructed. Simultaneously, the expression levels of hub genes were measured via qRT-PCR.ResultsThe results in this study indicated that 76 miRNAs, 1373 lncRNAs, and 4813 mRNAs were differentially expressed in SCII. A SCII-related ceRNA network was constructed with 154 ncRNAs, 139 mRNAs, and 51 miRNAs. According topological analysis, six lncRNAs (NONRATT019236.2, NONRATT009530.2, NONRATT026999.2, TCONS_00032391, NONRATT023112.2, and NONRATT021956.2) were selected to establish the ceRNA-pathway network, and then two candidate hub lncRNAs (NONRATT009530.2 and NONRATT026999.2) were identified. Subsequently, two lncRNA-miRNA-mRNA regulatory axes were identified. NONRATT026999.2 and NONRATT009530.2 might involve SCII via miR-20b-5p/Map3k8 axis based on the complex ceRNA network. SP1 and Hnf4a acting as important TFs might regulate Map3k8. Furthermore, qRT-PCR results showed that the NONRATT009530.2, NONRATT026999.2, Map3k8, Hfn4a, and SP1 were significantly upregulated in SCII of rats, while the miR-20b-5p was downregulated.ConclusionOur results offer a new insight to understand the ceRNA regulation mechanism in SCII and identify highlighted lncRNA-miRNA-mRNA axes and two key TFs as potential targets for prevention and treatment of SCII.
Highlights
Spinal cord ischemia/reperfusion injury (SCII) is a catastrophic complication result from cardiovascular, spine, and thoracic surgeries and can lead to paraplegia (Wang X. et al, 2019; Fang et al, 2020)
Multiple pathological changes can result in SCII including oxidative stress, blood spinal cord barrier (BSCB), neuroinflammation, neuronal apoptosis, and autophagy, which are related with the occurrence and progression of SCII
We found that one long non-coding RNAs (lncRNAs) or one miRNA connected with different mRNAs, while one mRNA connected with several miRNAs and lncRNAs
Summary
Spinal cord ischemia/reperfusion injury (SCII) is a catastrophic complication result from cardiovascular, spine, and thoracic surgeries and can lead to paraplegia (Wang X. et al, 2019; Fang et al, 2020). Multiple pathological changes can result in SCII including oxidative stress, blood spinal cord barrier (BSCB), neuroinflammation, neuronal apoptosis, and autophagy, which are related with the occurrence and progression of SCII Q. et al, 2016; Chen et al, 2020a,b) Inhibition of these damaging pathogeneses is widely assessed for treating spinal cord injury. Elaborating the molecular mechanism of SCII is important for clinical practice. Spinal cord ischemia/reperfusion injury (SCII) is a catastrophic complication involved with cardiovascular, spine, and thoracic surgeries and can lead to paraplegia. The molecular mechanism of SCII remain ill-defined
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