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Αλέξανδρος Γ. Σφακιανάκης

Tuesday, July 27, 2021

Regulation of the long noncoding RNA XIST on the inflammatory polarization of microglia in cerebral infarction

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Exp Ther Med. 2021 Sep;22(3):924. doi: 10.3892/etm.2021.10356. Epub 2021 Jun 30.

ABSTRACT

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, counterac ting 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.

PMID:34306193 | PMC:PMC8281447 | DOI:10.3892/etm.2021.103 56

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