Hsa_circ_0049472 contributed to amyloid-beta peptide-induced neurotoxicity, apoptosis and inflammation via regulating PI3K-AKT signaling pathway by interacting with miR-22-3p/ZNF217 axis

Background: Circular RNAs (circRNAs) exhibited important roles in Alzheimer's disease (AD). Here, we focused on the dysregulation of hsa_circ_0049472 (circ_0049472) and potential functions in SK-N-SH cells with amyloid-beta peptide (Aβ) treatment in AD.

Methods: RNA expression was detected by real-time quantitative PCR. Cell viability and proliferation were measured by MTS and Edu assays. Flow cytometry was used for Apoptosis detection, and cell inflammation was assessed using enzyme-linked immunosorbent assay. Target interaction was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. Protein expression and phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) pathway were examined by Immunoblotting.

Results: Aβ treatment inhibited cell viability and proliferation of SK-N-SH cells, but enhanced Apoptosis rate, Apoptosis protein levels (Bcl2-associated X protein and cleaved-caspase-3) and inflammatory cytokines (interleukin -6, IL-1β, tumor necrosis factor-α). Then, circ_0049472 expression was shown to be upregulated in response to Aβ stimulation and knockdown of circ_0049472 has ameliorated Aβ-induced cell injury. Circ_0049472 was identified as a Sponge for miR-22-3p, and miR-22-3p inhibition reversed the regulation of circ_0049472 knockdown in Aβ-treated cells. Furthermore, ZNF217 acted as a target of miR-22-3p and circ_0049472 could regulate ZNF217 expression via binding to miR-22-3p. Overexpression of miR-22-3p abated Aβ-induced Apoptosis and inflammation via downregulating ZNF217. Furthermore, Aβ reduced proteins levels of p-PI3K and p-AKT, and this inhibition of PI3K-AKT pathway was restored by the regulation of circ_0049472/miR-22-3p/ZNF217 axis.

Conclusion: Circ_0049472 was involved in Aβ-induced neural injury by regulating miR-22-3p/ZNF217 axis to affect PI3K-AKT pathway. This study has discovered an innovative mechanism for AD.

Aβ; Circ_0049472; MiR-22–3p; ZNF217.