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.

星形胶质细胞至关重要地参与神经退行性疾病和脑癌的发展。在这项工作中，我们调查了microRNA-194-5p（miR-194-5p）对脂多糖（LPS）诱导的星形胶质细胞活化及其潜在机制的潜在改善作用。用miR-194-5p模拟物或抑制剂转染星形胶质细胞，然后用LPS诱导。使用MTT测定法测量细胞增殖，而使用Transwell测定法评估细胞迁移。用酶联免疫吸附法测定环氧合酶2（COX2）和细胞因子（肿瘤坏死因子-α（TNF-α），转化生长因子β（TGF-β），白介素（IL）-1β和IL-6）的浓度。分析（ELISA）。通过定量逆转录PCR（RT-qPCR）评估基因表达，而蛋白质印迹法则用于定量相对蛋白表达。我们发现在LPS诱导的星形胶质细胞中下调的miR-194-5p显着抑制了LPS诱导的细胞增殖和迁移。另外，miR-194-5p抑制了COX2和促炎细胞因子（TNF-α，TGF-β，IL-1β和IL-6）的释放。此外，沉默神经氨酸亲和素1（NXPH1）是miR-194-5p的计算机化和通过机械方法确定的直接靶标，恢复了miR-194-5p的抗炎，抗增殖和抗迁移作用。我们预期miR-194-5通过直接靶向NXPH1抑制LPS诱导的星形胶质细胞的增殖，侵袭和炎症反应。这些发现提示，miR-194-5p / NXPH1轴在星形胶质细胞激活和神经炎症相关疾病中发挥重要作用。这一发现将为生物医学和神经科学研究开辟新的途径。