Recent studies have identified neuroinflammation as a significant contributor to the pathological process of traumatic brain injury (TBI) and as a potentially effective target for treatment. LncRNA maternally expressed gene 3 (Meg3) has further been observed to play a critical role in diverse biological processes, including microglial activation and the inflammatory response. However, its target gene and associated signaling pathway require further elucidation. This study found that lipopolysaccharide + ATP upregulated Meg3, promoted microglia activation, Nlrp3/caspase1 activation and inflammation, and markedly reduced miR-7a-5p. Overexpression of miR-7a-5p attenuated Meg3-induced microglial activation, but not Meg3 expression. Bioinformatic analysis and dual-luciferase assays indicated that Meg3 was a direct target of miR-7a-5p that negatively regulates miR-7a-5p expression. Further, we showed that Meg3 acted as a competing endogenous RNA for miR-7a-5p and induced microglial inflammation by regulating nod-like receptor protein 3 (Nlrp3) expression. Our study thus demonstrates Meg3 regulates microglia inflammation by targeting the miR-7a-5p /Nlrp3 pathway.
Keywords: Inflammation; LncRNA-Meg3; Microglia; Nlrp3 inflammasome; miR-7a-5p.
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