| Background and Purpose: Parkinson’s disease(PD)is a chronic and progressive extrapyramidal disease,and its complexity is still evolving.Whether it is about the diagnosis technology or the treatment effect of PD,it has not yet met the needs of both doc tors and patients.Classic symptoms of dyskinesia and slow progression of the disease form the main diagnostic basis of PD.In the absence of objective detection indicators,50%-70% of dopaminergic neurons in substantia nigra of midbrain have died when patients are diagnosed.Nowadays,as a star molecule in the field of biological research,mi RNA combines with its target gene m RNA through sequence complementary pairing to regulate gene expression at the post transcriptional level.The derived mi RNA-Gene regulatory network is gradually favored by scientists.However,up to now,little is known about the network regulation of PD functional mi RNA molecules and target genes.High throughput detection methods and techniques have been used to explore the mechanism of various diseases including PD.The purpose of this study is to analyze the mi RNA-Gene network regulation and screen the factors that may be related to PD,so as to further understand the molecular mechanism of PD.Methods: Firstly,this study collected the peripheral blood of three patients with confirmed PD and three normal people,and performed high-throughput sequencing to obtain PD-related mi RNA expression profiles.The data was cleaned out of the top five mi RNAs that were differentially expressed up and down with PD.mi RNA binding site mi RWalk database was used to predict the target genes of these ten mi RNAs,and then performed GO and KEGG analysis of the target genes.Secondly,we searched the GEO database to obtain the gene expression profiles of 40 PD samples and 53 control samples.After the data was cleaned,the DEGs and pivot genes were selected via the limma package and the WGCNA package,respectively,and then performed GO and KEGG analysis of the DEGs,and GSEA was performed for the whole gene set.Next,we extracted the intersection genes of the target gene and the pivot gene to show that the two have cooperative expression.Finally,we cross-matched the mi RNA and the intersection genes,visualized the mi RNA-Gene regulatory network diagram via Cytoscape software,and used the plug-in Cytohubba to screen out the core node genes of the network as the result of preliminary screening.Results: 1.A total of 204 DEMs were obtained by high-throughput sequencing.The top five up-regulated mi RNAs were mi R-4638-3p,mi R-4747-5p,mi R-6785-5p,mi R-5009-5p and mi R-3200-5p;the top five down-regulated mi RNAs were mi R-6856-5p,mi R-488-3p,mi R-6794-5p,mi R-3170-5p and mi R-1306-5p.Go and KEGG analysis showed that the target genes of these ten mi RNAs were involved in the immune response,metabolic regulation and neural function.2.A total of 602 DEGs and 21 pivot genes were obtained by microarray expression profile.Go and KEGG a nalysis showed that DEGs were mainly involved in growth regulation,neural regulation and degenerative diseases.GSEA analysis showed that PD expression profile was involved in the regulation of apoptosis.3.After the intersection of target genes and pivot genes,21 co-expression genes were obtained,which were ATP 5F1,ATP8B1,COX5 A,DBT,DIP2 A,FGFR1,GTF2H3,HAUS2,LRRFIP1,MAT2 A,MCF2L,MCTS1,MYO1 C,MZT2B,POGZ,RBM6,RIOK3,SLC35E1,TAOK1,TMEM14 B,ZNF160.4.In this study,a regulatory network containing 85 mi RNA-Gene interaction pairs was successfully drawn by Cytoscape software,and the cytohubba plug-in analysis showed that the core node of the network is the gene TAOK1.Conclusion: This study prelimin arily believed that TAOK1 may be related to PD,and assumed that this gene may induce apoptosis through the p38/MAPK pathway to participate in the occurrence and progression of PD. |
