Traumatic Brain Injury

MEG3[LncRNA]

miR-7a-5p[miRNA]

Nlrp3[mRNA]

traumatic brain injury cells

Homo sapiens (human)

Int Immunopharmacol. 2021 Jan;90:107141. doi: 10.1016/j.intimp.2020.107141. Epub 2020 Nov 12.

LncRNA-Meg3 promotes Nlrp3-mediated microglial inflammation by targeting miR-7a-5p.

luciferase assay;

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.