LncRNA‑AK158273 suppresses lipopolysaccharide‑triggered autophagy by up‑regulation of Mst1 expression in microglia

Introduction The aim of the present study was to investigate the mechanism by which lncR-AK158273 regulates autophagy in lipopolysaccharide (LPS)-induced neuroinflammation cognitive impairment (LPS-NCI). Methods LPS was used to establish a mouse of neuroinflammation‑mediated cognitive dysfunction. Cognitive deficits in the LPS‑NCI model were assessed using the new-object recognition test and Y maze test. Immunohistochemistry and immunofluorescence were performed to evaluate neuronal injury and the expression of CD11b, phosphorylated (p)-tau, and total tau. ELISA was used to quantify the levels of TNF-α and IL-6. RT-qPCR and western blotting were applied to measure the mRNA expression of STK4 and lncR-AK158273, as well as the protein levels of Mst1 and autophagy-related proteins. In addition, si-lncR-AK158273 or pcDNA-lncRNA-AK158273 was transfected into LPS‑stimulated BV2 cells to explore the function of this lncRNA in autophagy. Autophagosomes were visualized by transmission electron microscopy. Autophagic flux was determined using mRFP-GFP-LC3 fluorescence tracing with chloroquine (CQ) treatment to block lysosomal degradation. Results The results showed that LPS markedly elevated the protein levels of CD11b, TNF-α, IL-6, p-tau, Aβ 1–42, and P62, while reduing Beclin-1 expression and the LC3II/LC3I ratio, thereby suppressing autophagy in both LPS‑NCI mice and LPS-stimulated BV2 cells ( P < 0.05). Futhermore, lncR-AK158273 and STK4(Mst1) were significantly upregulated in LPS‑NCI mice and LPS-treated BV2 cells. Follow-up experiments verified that lncR-AK158273 upregulates Mst1 expression upon LPS stimulation. Moreover, lncR-AK158273 suppressed LPS‑triggered microglial autophagy by increasing Mst1 level. Discussion lncR-AK158273 may inhibit microglial autograph via upregulation of Mst1 expression during LPS-induced neuroinflammation.