Circular RNA hsa_circ_0004381 Promotes Neuronal Injury in Parkinson's Disease Cell Model by miR-185-5p/RAC1 Axis.

The study aims to explore the molecular mechanism involved in Parkinson's disease (PD). Hsa_circ_0004381, microRNA-185-5p (miR-185-5p), and Rac family small GTPase 1 (RAC1) level were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Furthermore, cell viability and apoptosis rate were assessed by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2-related X protein (Bax), cleaved-caspase 3 (c-caspase 3), and RAC1 were determined by western blot assay. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). The ROS generation and LDH and SOD activity were detected by the corresponding kits. The binding relationship between miR-185-5p and hsa_circ_0004381 or RAC1 was predicted by Starbase and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Hsa_circ_0004381 and RAC1 were increased, and miR-185-5p was decreased in MPP+-triggered SK-N-SH cells. Moreover, hsa_circ_0004381 silencing promoted cell viability, and repressed apoptosis, inflammatory response, and oxidative stress in MPP+-treated SK-N-SH cells. The mechanical analysis suggested that hsa_circ_0004381 served as a sponge of miR-185-5p to affect RAC1 expression. Hsa_circ_0004381 could contribute to MPP+-triggered neuron injury by targeting the miR-185-5p/RAC1 axis, which provided a novel insight into the pathogenesis and treatment of PD.