Small RNA sequencing of circulating small extracellular vesicles microRNAs in patients with amyotrophic lateral sclerosis

Abstract

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.

Biogenesis, Isolation, and Detection of Exosomes and Their Potential in Therapeutics and Diagnostics

“…This dysregulation associated with neurodegeneration causing ALS could pave the way for the identification of potential biomarkers of the disease [ 187 ]. Similarly, Kim et al [ 188 ] studied small RNA sequencing of 18 ALS patients and 15 healthy individuals. It was found that five of the miRNAs are differentially expressed in the patients of ALS as compared to the healthy individuals.…”

“…Bioinformatic analysis revealed that these miRNAs interact with different sets of genes which are involved in pathogenies in ALS. So, these two miRNAs can serve as potential biomarkers for detecting ALS [ 188 ]. In another study by Saucier et al [ 189 ], it was found that miR-15a-5p could serve as a biomarker for the diagnosis of ALS, as miR-193a-5p is linked to the progression of ALS.…”

miRNAs: Targets to Investigate Herpesvirus Infection Associated with Neurological Disorders

“…This investigation showed a positive and negative regulation of miR-23c and miR-192-5p, respectively, in patients with ALS. The analysis of bioinformatics revealed that these miRNAs interact with different target genes and are involved in the biological processes of ALS [129]. Regarding Alzheimer's disease, miR-146a is constantly investigated.…”