CircRNA Expression Profile Of Manganese-Induced Parkinsonism Revealed By Microarray And CircRNA Regulatory Mechanism

Background: Manganese-induced parkinsonism is a serious and irreversible extrapyramidal system motor dysfunction induced by manganese poisoning,the clinical manifestations are similar to those of Parkinson's disease,once diagnosed,the patients' extrapyramidal damage is irreversible,and there is no specific treatment,therefore,it is of great significance to further understand the pathogenesis of manganese-induced parkinsonism,so as to help identify high-risk patients with manganese-induced parkinsonism in patients with early manganese exposure and provide new therapeutic targets for treatment.CircRNA is a stable,diverse and conserved new type of non-coding RNA,which is involved in the regulation of human genes and related to the occurrence and development of diseases.The purpose of this study is to understand whether there is a specific circRNA expression profile of manganese-induced parkinsonism and preliminarily discuss its possible role in the pathogenesis of manganese-induced parkinsonism,so as to provide a new potential opportunityfor the diagnosis and treatment of manganese-induced parkinsonism.At present,there are no studies on circRNAs of manganese-induced parkinsonism.Methods: We include patients in Guangxi workers' hospital and the first affiliated hospital of guangxi medical university from March 2017 to October2018,divided into manganese-induced parkinsonism group?group A?,manganese exposure without parkinsonism group?group B?,Parkinson's disease?group D?and normal control group?group C?according to the clinical evaluation.The functions of differentially expressed circRNAs were analyzed by bioinformatics analysis.Extracting circRNAs from Plasma for circRNA microarray detection,screening differentially expressed circRNAs,and verifying their expression levels by real-time fluorescence quantitative PCR?QRT-PCR?.Results: Through circRNA microarray,13617 Raw Data were obtained in each sample,and a total of 10145 circRNAs were obtained from each experimental group with differential expression compared with the normal group after screening.Results suggest the manganese-induced parkinsonism group and normal control group with significant differences 21 circRNA expression,the manganese exposure without parkinsonism group and normal control group 194 circRNA expression exists significant differences,and the parkinson's disease group and normal control group with significant difference among 139 circular RNA expression after further screening.To evaluate the circRNA attributes in the biological process,cellular component and molecular functions,and in pathways,we conducted GO analysis and pathway analysis for circRNAs gene symbols to speculate circRNA potential functions according to bioinformatics analysis,to predict circRNA's potential function in manganese-induced parkinsonism.Results show significant enrichment of GO items include the formation and growth of neurons,reverse transportation,synaptic function,andthe 4 significantly enriched signaling pathways were ergic gabasynapse,morphine addiction,serotonergic synapse,and retrograde endocannabinoid signaling,all of which were related to neurotransmitter transmission between synapses,suggesting that circRNAs may be related to the occurrence and development of manganese-induced parkinsonism.And we investigated potential miRNAs binding with circRNAs by using Arraystar's home-made miRNA target prediction software based on TargetScan and miRanda.In addition,we analyzed the results of chip detection and found that there were 21 circRNAs that significant differentially expressed in manganese-induced parkinsonism group,and in the group of manganese exposure without parkinsonism or Parkinson's disease.selecting the five circRNAs expressed in each group have obvious gradient change,the five circRNAs are hsa_circ₀000008,hsa_circ₀038416,hsa_circ₀054033,hsa_circ₀004738and hsa_circ₀001101,and further QRT-PCR quantitative validation of the five differentially expressed circRNAs.PCR results showed that four circRNAs were consistent with the expression of the original sample,and three of them were statistically significant: hsa_circ₀000008,hsa_circ₀038416,and hsa_circ₀004738.The three circRNAs were significantly expressed in the group of manganese-induced parkinsonism?P=0.02,0.008,0.016,P < 0.05?,and the expression was not statistic and the expression was not statistically significant in the group of manganese exposure,and hsa_circ₀ally significant in the group of mn-free disease,and hsa_circ₀000008 was significantly expressed in the group of Parkinson's disease?P=0.015,P < 0.05?.Conclusion: There was a specific circRNAs expression profile in manganese-induced parkinsonism and provided new potential targets and novel insights for the future diagnosis and treatment of manganese-induced parkinsonism.