Proinflammatory polarization of microglia aggravates brain injury in cerebral infarction. The present study focused on the role of long non-coding (lnc)RNA X-inactive specific transcript (XIST) in the phenotype modulation of microglia. It was revealed that lncRNA XIST was significantly upregulated in both a mouse cerebral infarction model induced by middle cerebral artery occlusion (MCAO) and an activated microglial model induced by oxygen/glucose deprivation (OGD). The overexpression of XIST enhanced the expression and release of pro-inflammatory mediators [such as tumor necrosis factor (TNF)-α, IL-6, and iNOS] in microglia. Culture supernatant from lncRNA XIST-overexpressed microglial cells induced the apoptosis of primary neurons, while TNF-α antibody counteracted this neurotoxic effect. LncRNA XIST served as a sponge for miR-96-5p, counteracting its inhibitory effect on IKKβ/NF-κB signaling and TNF-α production. Notably, TNF-α was positively regulated by XIST and in turn enhanced XIST expression in microglia. The lncRNA XIST-TNF-α feedback promoted the proinflammatory polarization of microglia, thereby exacerbating cerebral neuron apoptosis.
Keywords: inhibitor of nuclear factor κB kinase subunit β; long non-coding RNA X-inactive specific transcript; microRNA-96-5p; microglia; tumor necrosis factor-α.
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