Small RNA sequencing of circulating small extracellular vesicles microRNAs in patients with ALS

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. Researchers at the Seoul National University Hospital 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. These results suggest that circulating sEV from ALS patients have distinct miRNA profiles which may be potentially useful as a biomarker of the disease.

Enrichment map illustrating significantly over-represented pathways
(Gene Ontology biological process)

Figure 3

For the genes targeted by miR-23c (blue) and miR-192-5p (red), respectively. Enrichment results were mapped as a network of gene sets (nodes) which are grouped together as a subnetwork by their shared genes. Node size is proportional to the total number of genes within each gene set. Edge represents the gene overlap between gene sets, and its thickness is proportional to size of the overlap.

Kim JA, Park C, Sung JJ, Seo DJ, Choi SJ, Hong YH. (2023) Small RNA sequencing of circulating small extracellular vesicles microRNAs in patients with amyotrophic lateral sclerosis. Sci Rep 13(1):5528. [article]

Leave a Reply

Your email address will not be published. Required fields are marked *