Circ_0092222 is Enhanced in Alzheimer's Disease and Exacerbates Aβ-induced Neurotoxicity Through Sponging miR-331-3p

This study aimed to explore the expression pattern of circ_0092222 in Alzheimer's disease (AD) and its role in Aβ-induced neuronal apoptosis. circ_0092222 was identified from the GEO dataset. Serum level of circ_0092222 in 95 AD patients and 100 controls was detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). AD cell model was achieved by treating SH-SY5Y cells with Aβ25-35. Cell viability, cytotoxicity, apoptosis and inflammation were detected. The targeting relationship between circ_0092222 and miR-331-3p, and between miR-331-3p and SEC61A1 was verified by the dual-luciferase reporter gene assay. Pearson correlation and Logistic regression analysis were used to evaluate the relationship between variables and the risk factors for AD progression. Circ_0092222 expressions in AD patients were higher than that in the control group. Short years of education, low mini mental state examination (MMSE) score, low plasma Aβ42/40 ratio, and elevated circ_0092222 were independent risk factors for the progression of mild AD to moderate/severe. In cell experiments, the expression of circ_0092222 was upregulated. Knockdown of circ_0092222 could significantly reduce the apoptosis rate, lactate dehydrogenase (LDH) release, pro-inflammatory cytokine levels, and the expressions of Bax and cleaved caspase-3, and increase cell viability and Bcl-2 expression. Bioinformatics prediction and dual-luciferase reporter gene assay confirmed that circ_0092222 directly binds to miR-331-3p, and miR-331-3p directly targets SEC61A1. Functional rescue experiments demonstrated that circ_0092222 regulates Aβ25-35-induced neuronal injury by up-regulating SEC61A1 through sponging miR-331-3p. Inhibiting circ_0092222 can improve Aβ25-35-induced apoptosis and inflammation, suggesting that circ_0092222 may be a potential target for AD treatment.