Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Sci Rep. 2023 Apr 4;13(1):5528. doi: 10.1038/s41598-023-32717-y.
Dysregulation of microRNAs (miRNA) in small extracellular vesicles (sEV) such as exosomes have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Although circulating cell-free miRNA have been extensively investigated in ALS, sEV-derived miRNAs have not been systemically explored yet. Here, we performed small RNA sequencing analysis of serum sEV and identified 5 differentially expressed miRNA in a discovery cohort of 12 patients and 11 age- and sex-matched healthy controls (fold change > 2, p < 0.05). Two of them (up- and down-regulation of miR-23c and miR192-5p, respectively) were confirmed in a separate validation cohort (18 patients and 15 healthy controls) by droplet digital PCR. Bioinformatic analysis revealed that these two miRNAs interact with distinct sets of target genes and involve biological processes relevant to the pathomechanism of ALS. Our results suggest that circulating sEV from ALS patients have distinct miRNA profiles which may be potentially useful as a biomarker of the disease.
微小 RNA（miRNA）在小细胞外囊泡（sEV）中的失调，如外泌体，与肌萎缩侧索硬化症（ALS）的发病机制有关。虽然循环无细胞 miRNA 在 ALS 中已经被广泛研究，但 sEV 衍生的 miRNA 尚未被系统地探索。在这里，我们对血清 sEV 进行了小 RNA 测序分析，在 12 名患者和 11 名年龄和性别匹配的健康对照组的发现队列中鉴定了 5 个差异表达的 miRNA（倍数变化 > 2，p < 0.05）。其中两个（miR-23c 和 miR192-5p 的上调和下调）在一个单独的验证队列（18 名患者和 15 名健康对照组）中通过液滴数字 PCR 得到了证实。生物信息学分析表明，这两个 miRNA 与不同的靶基因集相互作用，并涉及与 ALS 发病机制相关的生物学过程。我们的结果表明，来自 ALS 患者的循环 sEV 具有独特的 miRNA 谱，可能作为疾病的生物标志物具有潜在的应用价值。
