Exosomal miR-320e is a potential target of CVSD that regulates the Wnt2-mediated Wnt/β-catenin signaling pathway

Abstract Exosomal miRNAs play crucial roles in many central nervous system diseases. Cerebral small vessel disease (CVSD) is a small vessel disease thatis affected by various factors. In the present study, we investigated the role of exosomal miR-320e in theWnt/β-catenin pathway stimulated by oxidative stress and assessed its role in CVSD. The differentially expressed exosomal miRNAs were filtered by sequencing plasma exosomes from CVSD patients and healthy controls. Bioinformatic and dual luciferase analyses were used to confirm the relationship between Wnt2 and miR-320e. Quantitative real-time PCR and Western blotting were used to detect the mRNA and protein levels of Wnt/β-catenin pathway components. Membrane fluorescence staining was used to detect exosome transfer. High-throughput sequencing showed that exosomal miR-320e was downregulated. Bioinformatics analysis and dual-luciferase reporter gene experiments showed that exosomal miR-320e regulated Wnt2expression by targeting the 3' noncodingregion of Wnt2. Exosomal miR-320e was found to mediate the response of the Wnt/β-catenin signaling pathway to oxidative stress through loss-of-function experiments using mimics, inhibitors and knockdown/overexpression lentivirus. Exosomal miR-320e could target and inhibit the Wnt2/β-catenin signaling pathway. Our research suggests that exosomal miR-320e is a suppressor of the Wnt/β-catenin signaling pathway and may play a protective role in the progression of CVSD. Clinical trial registration Not applicable