The Potential Circular RNAs Biomarker Panel and Regulatory Networks of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disease. It has been reported that circular RNAs (circRNAs) play important roles in several neurological diseases. However, the role and regulatory networks of circRNAs in PD are still largely unclear. In this study, we first compared the global expression level of circRNAs from patients with PD and controls using microarray, then the candidate circRNAs were validated in another PD cohort. The possible functions of these candidate circRNAs were analyzed using Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the regulatory networks of these candidate circRNAs were constructed through circRNA–miRNA–mRNA regulatory networks, protein–protein interaction (PPI) networks, and transcription factor-circRNA networks. The results indicated that hsa_circRNA_101275, hsa_circRNA_103730, and hsa_circRNA_038416 were significantly more highly expressed in patients with PD, while hsa_circRNA_102850 was lower expressed in patients with PD when compared with controls. A circRNA panel combining the four differentially expressed circRNA showed a high diagnostic ability to distinguish patients with PD from controls (AUC = 0.938). Furthermore, GO and KEGG analysis showed these candidate circRNAs were enriched in PI3K–Akt and MAPK signaling pathways. We established circRNA–miRNA–mRNA regulatory networks and identified 10 hub genes (ESR1, PTEN, SHC1, IGF1R, SMAD2, KRAS, MDM2, HIF1A, BMP4, and ACVR2B) were closely related to PD by using PPI network analysis. Besides, these circRNAs were predicted to be regulated through tyrosine hydroxylase (TH)-relevant transcription factors such as GATA2 and GATA3. In conclusion, our results suggest that the circRNA panel and the established circRNA–miRNA–mRNA regulation networks might provide potential novel biomarkers and therapeutic targets for PD.

Brain alarm by self-extracellular nucleic acids: from neuroinflammation to neurodegeneration

“…In peripheral blood of PD patients 139 differentially expressed circRNAs were identified. Of them, 78 circRNAs were upregulated, whereas 61 were downregulated [ 417 ]. A total of 10 candidate circRNAs (five upregulated and five downregulated) were retrieved for further verification in a larger cohort.…”

“…A total of 10 candidate circRNAs (five upregulated and five downregulated) were retrieved for further verification in a larger cohort. Of these circRNAs, circ_103730, circ_101275, and circ_038416 were upregulated, while circ_102850 was downregulated in patients with PD when compared to healthy controls [ 417 ]. Similarly, a remarkably differently expressed circRNA landscape was found in plasma samples of PD patients and healthy controls [ 472 ].…”

The emerging role of circular RNAs in Parkinson’s disease

“…Compared with controls, hsa_circRNA_101275, hsa_circRNA_103730, and hsa_circRNA_038416 had significantly higher expression in PD patients, and hsa_circRNA_102850 had lower expression in PD patients. A circRNA panel containing the four differentially expressed circRNAs had a strong diagnostic capacity (area under the curve = 0.938) for distinguishing PD patients from controls (Xiao et al, 2022).…”

Early-stage idiopathic Parkinson’s disease is associated with reduced circular RNA expression

“…Their reported resistance to RNA exonuclease activity and increased stability compared to their linear counterparts 57 , 58 , have prompted investigations of their potential use as biomarkers in a range of human diseases, including PD 59 , 60 . Differential expression of circRNAs in PD has been reported 59 – 65 . However, these studies typically use small cohorts, identify specific circRNAs that are not replicated and show limited classification ability when compared to existing clinical predictors.…”