Category: Parkinsonism, Atypical: MSA
Objective: The discriminatory peripheral circulating small non-coding RNAs (sncRNAs) using next-generation sequencing (NGS) between patients of multiple system atrophy (MSA), Parkinson’s disease (PD), and healthy controls (HCs) were identified and validated in a cellular model of MSA.
Background: The roles of various sncRNAs, mostly microRNA (miRNA), as biomarkers to differentiate MSA with PD and HCs remain elusive.
Method: Participants were recruited in 2018 and 2019, labeled as discovery and testing cohorts, respectively. Differentially expressed (DE) circulating miRNAs profiled by NGS-based RNAseq were identified when those miRNA were both presented in two cohorts. MSA-associated miRNA were individually validated in a MSA cellular model using an alpha-synuclein-overexpressed MO3.13 oligodendroglial cell line.
Results: Overall, 160 patients (discovery cohort: 10 MSA, 41 PD, 17 HC; validation cohort: 38 MSA, 38 PD, 16 HC) were enrolled. MSA-associated miRNAs including five upregulated and eight downregulated miRNAs, and one downregulated piRNA were identified in both cohorts. Among them, three down regulated miRNAs have been previously identified in human cerebrospinal fluid. The in silicon analysis revealed that those putative MSA-associated miRNAs were largely involved in synaptic signaling and synaptogenesis. The functional roles of MSA-associated miRNAs were further examined in disease-relevant biological pathways including alpha-synuclein aggregation by treating miRNA-sponge in the MO3.13 cell line.
Conclusion: A list of novel circulating MSA-associated sncRNAs was identified by an untargeted NGS-based RNAseq. Those MSA-associated sncRNAs are beyond those previously derived from real-time quantitative PCR or microarray studies. Although the validation study of sncRNAs in the MSA cell model is challenging, further translational studies in animal models are ongoing.
To cite this abstract in AMA style:
MC. Kuo, SP. Lin, RM. Wu. Next-generation sequencing analysis of circulating microRNAs in multiple system atrophy [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/next-generation-sequencing-analysis-of-circulating-micrornas-in-multiple-system-atrophy/. Accessed June 15, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/next-generation-sequencing-analysis-of-circulating-micrornas-in-multiple-system-atrophy/