CircDLGAP4 overexpression ameliorates neuronal injury in Parkinson's disease by binding to EIF4A3 and increasing HMGA2 expression

Abstract

AbstractParkinson's disease (PD) is a prevalent neurodegenerative disease, and its prevalence increases steadily with age. Circular RNAs (circRNAs) are involved in various neurodegenerative diseases. Here, we aimed to explore the role of circRNA DLG‐associated protein 4 (circDLGAP4) in 1‐methyl‐4‐phenylpyridinium ion (MPP+)‐induced neuronal injury in PD. SH‐SY5Y cells were treated with MPP+ to establish PD cell models. The levels of circDLGAP4 and high mobility group AT‐hook 2 (HMGA2) in SH‐SY5Y cells were detected. SH‐SY5Y cell viability and apoptosis were detected. The levels of inflammatory damage (IL‐1β, IL‐6, TNF‐α) and oxidative stress (reactive oxygen species, lactate dehydrogenase, superoxide dismutase, and malondialdehyde)‐related factors were measured. The binding of eukaryotic initiation factor 4A3 (EIF4A3) to circDLGAP4 and HMGA2 was analyzed using RNA pull‐down or RNA immunoprecipitation. The stability of HMGA2 was detected after actinomycin D treatment, and its effects on neuronal injury were tested. CircDLGAP4 expression was decreased in MPP+‐induced SH‐SY5Y cells. CircDLGAP4 upregulation restored cell activity, decreased apoptosis, and reduced inflammatory damage and oxidative stress in PD cell models. CircDLGAP4 bound to EIF4A3 to increase HMGA2 expression and stability. Silencing HMGA2 attenuated the protective effect of circDLGAP4 overexpression. Overall, circDLGAP4 upregulated HMGA2 by recruiting EIF4A3, thus increasing the mRNA stability of HMGA2 and alleviating neuronal injury in PD.