Identification of a circRNA-miRNA-mRNA interactome associated with Parkinson's disease progression

BackgroundCircular RNAs (circRNAs) constitute a distinctive subclass of RNAs that are known for their regulatory roles in fundamental cellular processes. Due to their increased stability and ubiquitous expression, circular RNAs have been widely studied as potential molecular targets in various diseases, including neurodegenerative diseases. While several studies have found differentially expressed circRNAs associated with Parkinson's disease (PD), none has looked specifically into PD progression.ObjectiveTo elucidate the role of circRNAs in the progression of PD by identifying dysregulated circRNAs associated with PD progression and to pinpoint potential downstream miRNAs and associated differentially expressed gene targets.MethodsIn this study, we have utilized large-scale, longitudinal, and deep RNA-seq data from two independent cohorts, namely the Parkinson's Progression Marker Initiative (PPMI) and the Parkinson's Disease Biomarker Program (PDBP), to characterize circRNA expression in patients of early PD stage.ResultsWe identified six circRNAs significantly differentially expressed in whole blood samples obtained from PD patients over time. Additionally, we were able to map a competing endogenous RNA (ceRNA) network with potential downstream miRNA-mRNA targets and, with the help of co-expression analysis, to identify genes associated with PD progression. Our findings provide compelling evidence for a dysregulated circRNA interactome as an indicator of PD progression, with changes in the expression of these circRNAs and downstream gene targets being significantly associated with changes in UPDRS III scores in PD patients.ConclusionsOur results strongly indicate the association of circular RNAs with PD progression and emphasize its significance as a critical molecular marker.