STAG2 Alleviates Anxiety Disorder via Inhibiting cGAS-STING Pathway

Anxiety is one of the most common mental disorders. We aim to find novel biomarkers to explore its potential mechanism in anxiety disorders. Differentially expressed genes (DEGs) were screened out from GSE29014 and GSE100084 datasets. Protein-protein interaction network, enrichment analysis, and principal component analysis were employed to determine hub genes. The anxiety model was constructed by restraint stress. Behavioral tests, enzyme-linked immunosorbent assay, hematoxylin-eosin, and Nissl staining were applied to evaluate the anxiety model. The potential mechanisms were investigated by corticosterone (CORT)-induced PC12 cells as an in vitro model. Proteins and mRNA expression levels were measured by western blot and real-time quantitative polymerase chain reaction. Cell counting kit, 5-Ethynyl-2'-deoxyuridine, and flow cytometry assays were employed to measure proliferation and apoptosis. PTPRC, SMC3, STAG2, FLT3, SYNE1, TERF2IP, NIPBL, ZFP451, MLLT3, and JAK1 were identified as hub genes with high prediction value for anxiety. Hippocampal neurons were damaged with decreased 5-hydroxytryptamine, γ-amino butyric acid, and neuropeptide Y, as well as increased corticotrophin releasing factor and cholecystokinin in anxiety model. PTPRC, SMC3, STAG2, SYNE1, NIPBL, and ZFP451 were downregulated in anxiety mice. STAG2 was selected as the research target. In CORT-induced PC12 cells, STAG2 overexpression promoted cell proliferation, while inhibiting apoptosis and the expression of proteins in cGAS-STING pathway. STAG2 is a potential biomarker of anxiety that exerts a neuroprotective effect on CORT-induced PC12 cells via suppressing cGAS-STING pathway.