CircARID1B Promotes MPP+-Induced Death and Inflammation in Dopaminergic Neurons by Elevating MAVS Through Sequestering miR-143-3p.

Abstract

Increasing evidence has shown the involvement of abnormal circRNA in neurodegenerative disease progression, including Parkinson's disease (PD). Hence, this work focused on probing the function and mechanism of circARID1B on PD progression.1-Methyl-4-phenylpyridinium (MPP+)-induced human dopaminergic SK-N-AS neuroblastoma cell models were used to mimic PD injury in vitro. qRT-PCR and western blotting analyses were used to detect the levels of genes and proteins. Cell death was evaluated by cell counting kit-8 assay, flow cytometry, and lactate dehydrogenase (LDH) activity. Oxidative stress was analyzed by measuring the production of reactive oxygen species (ROS) and superoxide dismutase (SOD). Cell inflammation was determined by ELISA analysis. The binding between miR-143-3p and circARID1B or mitochondrial antiviral signaling protein (MAVS) was analyzed by dual-luciferase reporter and RNA immunoprecipitation assays. A high circARID1B expression was observed in MPP⁺ treated SK-N-AS cells. Functionally, circARID1B deficiency suppressed MPP⁺-induced apoptosis, LDH release, oxidative stress and inflammatory response in SK-N-AS cells. Mechanistically, circARID1B bound to miR-143-3p, which was reduced in SK-N-AS cells after MPP⁺ treatment. Moreover, miR-143-3p inhibition reversed the protective effects of circARID1B silencing on MPP⁺-treated SK-N-AS cells. Subsequently, we confirmed miR-143-3p directly targeted MAVS. MAVS was increased in SK-N-AS cells after MPP⁺ treatment. Moreover, MAVS overexpression abolished miR-143-3p up-regulation-induced inhibition of cell apoptosis, LDH release, oxidative stress and inflammation. CircARID1B deficiency suppressed MPP+-induced neural death and inflammation by miR-143-3p/MAVS axis, which may offer an improved understanding of PD progression and be useful for the development of circRNA-based therapy in PD.