MicroRNA-23a-3p Is Upregulated in Plasma Exosomes of Bulbar-onset ALS Patients and Targets ERBB4

• Published in: Neuroscience Vol. 524; pp. 65 - 78
• Main Authors: Liu, Yue, Ding, Man, Pan, Sijia, Zhou, Rumeng, Yao, Jiajia, Fu, Rong, Yu, Hang, Lu, Zuneng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.08.2023
• Subjects: amyotrophic lateral sclerosis; apoptosis; bulbar-onset ALS; ERBB4; exosome; MicroRNA-23a-3p; sALS; EVs; bulbar-onset ALS; ERBB4; ALS; apoptosis; HCs; EDTA; amyotrophic lateral sclerosis; exosome; MicroRNA-23a-3p
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2023.05.030

[Display omitted] •MicroRNA expression profile of plasma exosomes from bulbar-onset ALS patients.•52 miRNAs were upregulated in the ALS population by Small RNA sequencing.•miR-23a-3p was increased in bulbar-onset ALS patients.•The dysregulation of miR-23a-3p influenced cells survival. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease related to the progressive death of motor neurons. Understanding the pathogenesis of ALS continues to provide considerable challenges. Bulbar-onset ALS involves faster functional loss and shorter survival time than spinal cord-onset ALS. However, debate is ongoing regarding typical plasma miRNA changes in ALS patients with bulbar onset. Exosomal miRNAs have not yet been described as a tool for bulbar-onset ALS diagnosis or prognosis prediction. In this study, candidate exosomal miRNAs were identified by small RNA sequencing using samples from patients with bulbar-onset ALS and healthy controls. Potential pathogenic mechanisms were identified through enrichment analysis of target genes for differential miRNAs. Expression of miR-16-5p, miR-23a-3p, miR-22-3p, and miR-93-5p was significantly up-regulated in plasma exosomes from bulbar-onset ALS patients compared with healthy control subjects. Among them, miR-16-5p and miR-23a-3p were significantly lower in spinal-onset ALS patients than those with bulbar-onset. Furthermore, up-regulation of miR-23a-3p in motor neuron-like NSC-34 cells promoted apoptosis and inhibited cell viability. This miRNA was found to directly target ERBB4 and regulate the AKT/GSK3β pathway. Collectively, the above miRNAs and their targets are related to the development of bulbar-onset ALS. Our research indicates that miR-23a-3p might have an effect on motor neuron loss observed in bulbar-onset ALS and may be a novel target for the therapy of ALS in the future.