Circ_0049472 downregulation relieves Amyloid-β-induced neuronal injury by modulating PDE4A expression via targeting miR-22-3p in Alzheimer's disease.

Abstract

Neuronal injury is a common event in the development of Alzheimer's disease (AD). Previous studies have suggested that circular RNAs (circRNAs) are involved in neuronal injury in the pathological progression of AD. However, the potential role of circ_0049472 in the AD process is still unclear. Amyloid-β (Aβ)-treated SK-N-SH and CHP212 cells were used as the cell model of AD in vitro. The expression of circ_0049472, miR-22-3p, and phosphodiesterase 4A (PDE4A) was measured by quantitative real-time PCR (qPCR). Cell viability, proliferation, and apoptosis were estimated by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, and flow cytometry assay. Proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (bcl-2), Bcl-2 related X protein (bax), cleaved-caspase 3, PDE4A, and Postsynaptic protein-95 (PSD-95) were determined using western blot. Interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α) levels were analyzed using enzyme-linked immunosorbent assay (ELISA). JC-1 assay was utilized to evaluate mitochondrial function. Binding between miR-22-3p and circPLAR1 or PDE4A was predicted and verified using dual-luciferase reporter assay or RNA Immunoprecipitation (RIP) assay. Circ_0049472 and PDE4A were overexpressed in Aβ-treated SK-N-SH and CHP212 cells, and miR-22-3p was reduced. Knockdown of circ_0049472 might abolish Aβ-mediated proliferation inhibition and the promotion of apoptosis and inflammation, mitochondrial dysfunction in SK-N-SH and CHP212 cells. Mechanistically, circ_0049472 is competitively bound to miR-22-3p to elevate its target PDE4A. Circ_0049472 knockdown alleviated Aβ-induced SK-N-SH and CHP212 cell dysfunctions via targeting the miR-22-3p/PDE4A axis, suggesting that circ_0049472 knockdown might protect from neuronal injury in AD.