Journal
NEUROSCIENCE LETTERS
Volume 715, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2019.134649
Keywords
XIST; miR-27a; Spinal cord injury (SCI); LPS; Smurf1
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Spinal cord injury (SCI) is a devastating neuropathological condition. Long noncoding RNA X-inactive specific transcript (XIST) is an acknowledged cancer-related gene and participates in the development of SCI. However, role of XIST in SCI remains to be well revealed. Expression of XIST, miRNA-27a-3p (miR-27a) and smad ubiquitination regulatory factor 1 (Smurf1) was detected using RT-qPCR and western blotting. Cell apoptosis and inflammatory injury were assessed by sulforhodamine B (SRB) assay, flow cytometry, western blotting and enzyme-linked immunosorbent assay. The relationship among miR-27a, XIST and Smurf1 was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assay. As a result, we observed higher level of XIST and Smurf1, but lower level of miR-27a in SCI rats and lipopolysaccharide (LPS)-induced primary microglial cells. in vitro, LPS induced SCI microglia cells as described by decreased cell viability and B cell lymphoma 2 (Bel-2) expression, and increased cell apoptosis rate, Bax and cleaved caspase 3 levels, and tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) secretions, in vivo, a T10 laminectomy caused SCI rats as evidenced by decreased Basso-Beattie-Bresnahan Locomotor Rating Scale (BBB) score and induced expression of Bax, cleaved caspase 3, TNF-alpha and IL-6. However, silencing of XIST could mitigate the apoptosis and inflammatory injury in LPS-induced microglia and SCI rats. Mechanically, miR-27a interacted with XIST and Smurf1 via target binding. Either miR-27a downregulation or Smurf1 overexpression partially reversed the role of XIST deletion in LPS-treated microglial cells. Collectively, knockdown of XIST could alleviate the apoptosis and inflammatory injury of SCI models in vitro and in vivo through directly modulating miR-27a/Smurf1 axis.
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