Differentially Expressed Circular RNAs in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease

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.

Circulating CircRNAs Panel Acts as a Biomarker for the Early Diagnosis and Severity of Parkinson’s Disease

“…However, the expression of circRNA peripheral blood mononuclear cells of patients diagnosed with PD has been investigated. Among the six aberrantly expressed circRNA, four could distinguish PD from healthy control ( Ravanidis et al, 2021 ).…”

The Emerging Role of Circular RNAs in Alzheimer’s Disease and Parkinson’s Disease

“…Differentially expressed circRNAs in PBMCs have also been studied in PD patients and have been considered as possible biomarkers for the diagnosis of PD. Ravanidis et al ( 2021 ) enrolled 60 PD patients and 60 healthy controls to compare circRNA expression between the two groups via microarray analysis, which showed that six circRNAs were obviously decreased. In order to further evaluate the diagnostic value of the differentially expressed circRNAs in PD patients, receiver operating characteristic (ROC) curves were performed, and the area under the curve (AUC) was calculated to evaluate the predictive sensitivity and specificity of PBMC circRNAs for PD diagnosis.…”

Genetic and Transcriptomic Biomarkers in Neurodegenerative Diseases: Current Situation and the Road Ahead

“…For example, Cressatti et al, found that salivary miRNA-153 and miRNA-223 may be able to distinguish PD patients from controls with an area under the curve of 79% (95% confidence interval (CI), 64.5-99.2) and 74% (95% CI, 59.6-93.0), respectively [29]. Similarly, Ravanidis and colleagues identified six circRNAs that may be deregulated in PD patients [30]. The authors combined four of these into one biomarker, which in the same patients had a sensitivity of 75.3%, a specificity of 78%, and an area under the curve of 0.84.…”