Τίτλος:
Differentially Expressed Circular RNAs in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2021 Biomedical Research Foundation, Academy of Athens. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Συγγραφείς:
Ravanidis, S.
Bougea, A.
Karampatsi, D.
Papagiannakis, N.
Maniati, M.
Stefanis, L.
Doxakis, E.
Περιοδικό:
Movement Disorders
Εκδότης:
John Wiley and Sons Inc
Λέξεις-κλειδιά:
ataxin 2; biological marker; circular ribonucleic acid; fragile X mental retardation protein; levodopa; microRNA; RNA binding protein; RNA binding protein FUS; TAR DNA binding protein; FMR1 protein, human; fragile X mental retardation protein; microRNA, adult; Article; cohort analysis; computer assisted tomography; controlled study; cross linking; disease duration; down regulation; female; gene expression; gene expression regulation; gene ontology; human; human cell; major clinical study; male; Mini Mental State Examination; nuclear magnetic resonance imaging; onset age; Parkinson disease; peripheral blood mononuclear cell; priority journal; protein modification; real time reverse transcription polymerase chain reaction; Unified Parkinson Disease Rating Scale; genetics; mononuclear cell; Parkinson disease, Fragile X Mental Retardation Protein; Gene Ontology; Humans; Leukocytes, Mononuclear; MicroRNAs; Parkinson Disease; RNA, Circular
