Astrocytes are vitally involved in the development of neurodegenerative diseases and brain cancers. In this work, we investigated the potential ameliorative role of microRNA-194-5p (miR-194-5p) against lipopolysaccharide (LPS)-induced astrocytes activation and the mechanism underneath. Astrocytes were transfected with miR-194-5p mimic or inhibitor and subsequently induced with LPS. Cell proliferation was measured using MTT assay while Transwell assay was used for assessing cell migration. The concentrations of cyclooxygenase 2 (COX2) and cytokines (tumor necrosis factor-α (TNF-α), transforming growth factor β (TGF-β), interleukin (IL)-1β and IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Gene expression was assessed by quantitative reverse transcription PCR (RT-qPCR) while western blotting was used for quantifying relative protein expression. We found that miR-194-5p, downregulated in LPS-induced astrocytes, significantly inhibited LPS-induced cell proliferation and migration. In addition, miR-194-5p inhibited the release of COX2 and pro-inflammatory cytokines (TNF-α, TGF-β, IL-1β and IL-6). Moreover, the silencing of neurexophilin 1 (NXPH1), an in silico and mechanistically confirmed direct target of miR-194-5p, reverted the anti-inflammatory, anti-proliferative and anti-migratory effects of miR-194-5p. We anticipated that miR-194-5 inhibits the proliferation, invasion, and inflammatory reaction in LPS-induced astrocytes by directly targeting NXPH1. These findings hinted that miR-194-5p/NXPH1 axis exerts vital functions in astrocytes activation and neuroinflammation-associated diseases. This finding will open novel avenues for biomedical and neuroscience research.
Keywords: Astrocytes; Cell activation; Neurexophilin 1; Neuroinflammation; miR-194-5p.