Circular RNAs in Parkinson’s Disease: Reliable Biological Markers and Targets for Rehabilitation

小桶 下调和上调 康复 环状RNA 表观遗传学 基因 计算生物学 疾病 小RNA 生物信息学 发病机制 医学 生物 遗传学 基因表达 神经科学 基因本体论 病理
作者
Yinan Duan,Yixuan Wang,Yonghong Liu,Zhaohui Jin,Cui Liu,Xin Yu,Keke Chen,Detao Meng,Jianing Xi,Boyan Fang
出处
期刊:Molecular Neurobiology [Springer Nature]
卷期号:60 (6): 3261-3276 被引量:8
标识
DOI:10.1007/s12035-023-03268-0
摘要

In clinical practice, the underlying pathogenesis of Parkinson’s disease (PD) remains unknown. Circular RNAs (circRNAs) have good biological properties and can be used as biological marker. Rehabilitation as a third treatment alongside drug and surgery has been shown to be clinically effective, but biomarkers of rehabilitation efficiency at genetic level is still lacking. In this study, we identified differentially expressed circRNAs in peripheral blood exosomes between PD patients and health controls (HCs) and determined whether these circRNAs changed after rehabilitation, to explore the competing RNA networks and epigenetic mechanisms affected. We found that there were 558 upregulated and 609 downregulated circRNAs in PD patients compared to HCs, 3398 upregulated and 479 downregulated circRNAs in PD patients after rehabilitation compared to them before rehabilitation, along with 3721 upregulated and 635 downregulated circRNAs in PD patients after rehabilitation compared to HCs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially expressed circRNAs may affect the stability of the cellular actin backbone and synaptic structure by influencing the aggregation of α-synuclein (a-syn). We selected two circRNAs overexpressed in PD patients for validation (hsa_circ_0001535 and hsa_circ_0000437); the results revealed that their expression levels were all reduced to varying degrees (p < 0.05) after rehabilitation. After network analysis, we believe that hsa_circ_0001535 may be related to the aggregation of a-syn, while hsa_circ_0000437 may act on hsa-let-7b-5p or hsa-let-7c-5p through sponge effect to cause inflammatory response. Our findings suggest that rehabilitation can mitigate the pathological process of PD by epigenetic means.
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