Abstract
Long noncoding RNAs have been demonstrated to play crucial roles in the pathogenesis of spinal cord injury (SCI). In this study, we aimed to explore the roles and underlying mechanisms of lncRNA X-inactive specific transcript (XIST) in SCI progression. SCI mice model was constructed and evaluated by the Basso–Beattie–Bresnahan method. The SCI cell model was constructed by treating BV2 cells with lipopolysaccharide (LPS). The levels of XIST and miR-219-5p were determined by the reverse transcription quantitative polymerase chain reaction. The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Protein levels were measured via western blot assay. Cell viability and apoptosis were evaluated by cell counting kit-8 assay and flow cytometry analysis, respectively. The relationship between XIST and miR-219-5p was analyzed by online tool starBase, dual-luciferase reporter assay, and RNA immunoprecipitation assay. As a result, the XIST level was enhanced and the miR-219-5p level was declined in the SCI mice model. XIST was also upregulated in LPS-induced BV2 cells. LPS treatment restrained BV2 cell viability and accelerated apoptosis and inflammatory response. XIST knockdown effectively weakened LPS-induced BV2 cell injury. miR-219-5p was identified as a target of XIST. Moreover, inhibition of miR-219-5p restored the impacts of XIST knockdown on cell viability, apoptosis, and inflammation in LPS-treated BV2 cells. In addition, LPS-induced XIST promoted the activation of the nuclear factor-κB (NF-κB) pathway by sponging miR-219-5p. In conclusion, XIST silencing promoted microglial cell viability and repressed apoptosis and inflammation by sponging miR-219-5p, thus promoting the recovery of SCI.
Highlights
Long noncoding RNAs have been demonstrated to play crucial roles in the pathogenesis of spinal cord injury (SCI)
Zhou et al claimed that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) level was conspicuously raised in SCI mice and LPS-activated microglial cells, and MALAT1 knockdown relieved LPS-stimulated inflammatory injury by regulating miR-199b and IκB kinase β (IKKβ)/nuclear factor-κB (NF-κB) pathway [31]
The results showed that the hindlimb locomotor activity was markedly decreased after spinal cord contusions, as indicated by the decreased BBB score in SCI groups compared with sham operation groups (Figure 1a)
Summary
Long noncoding RNAs have been demonstrated to play crucial roles in the pathogenesis of spinal cord injury (SCI). (TUG1) repressed lipopolysaccharide (LPS)-stimulated PC-12 cell damage, as demonstrated by the promotion in cell viability and the suppression in cell apoptosis and inflammation, by decreasing miR-127 and inactivating nuclear factor-κB (NF-κB) pathway [30]. Zhou et al claimed that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) level was conspicuously raised in SCI mice and LPS-activated microglial cells, and MALAT1 knockdown relieved LPS-stimulated inflammatory injury by regulating miR-199b and IκB kinase β (IKKβ)/NF-κB pathway [31]. These reports indicated the vital roles of lncRNAs in SCI development. The relationship between XIST and miR-219-5p in regulating SCI progression has not been explored
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