CircNCOA4 knockdown attenuates OGD-induced neuron injury through miR-338-5p/PDE4B axis

Exp Brain Res. 2023 Sep 16. doi: 10.1007/s00221-023-06702-w. Online ahead of print.ABSTRACTCircular RNAs (circRNAs) have been revealed to be involved in the pathology of acute ischemic stroke (AIS). Herein, we aimed to study the role and mechanism of circNCOA4 in ischemic stroke. The neuron-like cell line SK-N-SH of the experiment group was cultured in oxygen-glucose deprivation (OGD) condition. Cell viability and apoptosis were evaluated by cell counting kit-8 and flow cytometry. The oxidative damage and endoplasmic reticulum stress (ERS) were analyzed by measuring the production of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and ERS-related markers. The binding between miR-338-5p and circNCOA4 or PDE4B (Phosphodiesterase 4B) was confirmed using dual-luciferase reporter and RIP assays. The commercial kit was used for exosome separation. The levels of circNCOA4 and PDE4B were increased, while miR-338-5p expression was decreased by OGD stimulation. OGD stimulation resulted in the apoptosis of neurons and induced oxidative damage and ERS, these effects were attenuated by circNCOA4 knockdown, while reinforced by circNCOA4 overexpression. Mechanistically, circNCOA4 acted as a sponge for miR-338-5p, and PDE4B was a target of miR-338-5p. MiR-338-5p inhibition reversed the neuroprotective effects of circNCOA4 silencing on neurons. Besides, miR-338-5p overexpression could abolish OGD-induced neuron injury, which was reversed by PDE4B upregulation...
Source: Experimental Brain Research - Category: Neuroscience Authors: Source Type: research