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

• Published in: International immunopharmacology 2021-01, Vol.90, p.107141-107141, Article 107141
• Main Authors: Meng, Jiao, Ding, Ting, Chen, Yuhua, Long, Tianlin, Xu, Quanhua, Lian, Wenqing, Liu, Wei
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - pharmacology; Animals; Biological activity; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain Injuries, Traumatic - genetics; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - pathology; Cells, Cultured; Head injuries; Inflammasomes - genetics; Inflammasomes - metabolism; Inflammation; Inflammatory response; Lipopolysaccharides; Lipopolysaccharides - pharmacology; LncRNA-Meg3; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Microglia - metabolism; Microglia - pathology; MicroRNAs - genetics; MicroRNAs - metabolism; miR-7a-5p; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Nlrp3 inflammasome; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Traumatic brain injury
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.107141

•LPS promoted microglia activation and inflammation, upregulated Meg3, and reduced miR-7a-5p.•Meg3 was a direct target of miR-7a-5p that negatively regulates miR-7a-5p expression.•Meg3/miR-7a-5p induced microglial inflammation by regulating Nlrp3 expression. 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.