Differentially Expressed Circular RNAs in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease
Open accessPublished version of a preprint
Abstract
Background: New noninvasive and affordable molecular approaches that will complement current practices and increase the accuracy of Parkinson's disease (PD) diagnosis are urgently needed. Circular RNAs (circRNAs) are stable noncoding RNAs that accumulate with aging in neurons and are increasingly shown to regulate all aspects of neuronal development and function. Objectives: Τhe aims of this study were to identify differentially expressed circRNAs in blood mononuclear cells of patients with idiopathic PD and explore the competing endogenous RNA networks affected. Methods: Eighty‐seven circRNAs were initially selected based on relatively high gene expression in the human brain. More than half of these were readily detectable in blood mononuclear cells using real‐time reverse transcription‐polymerase chain reaction. Comparative expression analysis was then performed in blood mononuclear cells from 60 control subjects and 60 idiopathic subjects with PD. Results: Six circRNAs were significantly down‐regulated in patients with PD. The classifier that best distinguished PD consisted of four circRNAs with an area under the curve of 0.84. Cross‐linking immunoprecipitation‐sequencing data revealed that the RNA‐binding proteins bound by most of the deregulated circRNAs include the neurodegeneration‐associated FUS, TDP43, FMR1, and ATXN2. MicroRNAs predicted to be sequestered by most deregulated circRNAs have the Gene Ontology categories “protein modification” and “transcription factor activity” mostly enriched. Conclusions: This is the first study that identifies specific circRNAs that may serve as diagnostic biomarkers for PD. Because they are highly expressed in the brain and are derived from genes with essential brain functions, they may also hint on the PD pathways affected. © 2021 Biomedical Research Foundation, Academy of Athens. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Cites
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“Due to the lack of free ends, which are normally targeted by 30 and 50 exoribonucleases, circRNAs are extremely stable with a half-life of more than 48 hours compared with approximately 6 hours for linear transcripts.(7,8) There are different subtypes of circRNAs, including exonic, intronic, and exo-intronic.”
BackgroundCircular RNAs are abundant, conserved, and associated with ALU repeats
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Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed
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“Eighty-seven circRNAs were carefully selected by cross-examining the data from three genome-wide surveys.(4,18,36) We chose circRNAs that had high expression in the brain (Rybak–Wolf score > 1,000) and low or no expression in other tissues.”
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Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients
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- Authors
- Ravanidis, S., Bougea, A., Karampatsi, D., Papagiannakis, N., Maniati, M., Stefanis, L., & Doxakis, E.
- Affiliations
- Academy of Athens (GR)
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Doxakis, Epaminondas
- ORCID
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2021-01-12
- Volume
- 36
- Issue
- 5
- Pages
- 1170-1179
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- PMC
- PMC8248110
- OpenAlex
- W3119420631
- Cited by
- 63
- References
- 9
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 11 · 2023: 15 · 2022: 10 · 2021: 9
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Movement Disorders (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- General Secretariat for Research and Innovation (2018∑Ε01300001, MIS 5049385)
- Michael J. Fox Foundation for Parkinson's Research (13353)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- Parkinson's disease, circular RNA, peripheral blood mononuclear cells, circRNA biomarkers, non-invasive diagnosis, competing endogenous RNA network, RNA-binding proteins, FUS, TDP-43, FMR1 gene, ATXN2, microRNA sequestration, differential gene expression
- MeSH terms
- RNA, Circular, Humans, Leukocytes, Mononuclear, Parkinson Disease, MicroRNAs, Gene Ontology
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