To Investigate The Expression And Clinical Significance Of MicroRNA In Different Cognitive Disorders Based On Bioinformatics Analysis

Objectives:Screening for differentially expressed micro RNA(DE-miRNA)in plasma of patients with different types of cognitive disorders,using bioinformatics analysis to predict target genes for DE miRNA and identify key genes,exploring the biological functions of DE-miRNA and key genes and finding potential biological targets for the diagnosis and treatment of different types of cognitive disorders is of great significance for delaying the development of the disease and improving the quality of life of patients.Methods:(1)This study included 24 subjects who were hospitalized or admitted to the Department of Neurology of our hospital from 2019 to 2022.Patients were divided into four groups according to whether they had cognitive impairment or not: post-stroke cognitive impairment(PSCI)group(n=6),post-stroke non-cognitive impairment(PSNCI)group(n=6),Alzheimer’s Disease group(AD)(n=6)and normal control group(NC)(n=6).General clinical data,neuropsychological assessment data and biological samples of the subjects were collected.(2)Plasma miRNA expression levels were detected by high-throughput sequencing.(3)DE-miRNA were screened by LIMMA ebayes method,Benjamini-Hochberg check and fold change(P<0.05,|log2FC|≥1).(4)Target genes of DE-miRNA were predicted by miRNet,Targetscan Human and miRDIP databases.(5)Functional enrichment analysis of the target genes was conducted using the gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG).STRING tools were used to construct the target gene-specific protein-protein interaction(PPI)network to analyze the potential relationships among proteins and search for key genes.(6)The DE-miRNA-key genes-signaling pathway network was constructed,and the roles of DE-miRNA and related genes and signaling pathways in AD and PSCI were inferred through comprehensive network construction and literature search.Results:1.AD compared with NC group,a total of 31 DE-miRNA(P<0.05,|log2FC|≥1),Including hsa-miR-4655-5p、hsa-miR-4478、hsa-miR-548as-5p、hsa-miR5186、hsa-miR-187-5p、hsamiR-3157-5p、hsa-miR-519c-3p etc.The target genes of the above DE-miRNA are mainly concentrated in Fox O、MAPK and PI3K-Akt signaling pathways.Combined with PPI network,10 key genes were predicted: ATM、MYC、PTEN、CDKN1B、CCNB1、HIF1A、CDK2、BMI1and IGF1 R.2.AD compared with PSCI group,a total of 22 screened DE-miRNA(P<0.05,|log2FC|≥1),including hsa-miR-6883-5-P、hsa-miR-449b-5P、hsa-miR-6868-3P etc.Target genes are enriched in cellular senescence、cell cycle、p53 and Hippo signal pathways.Three key genes CDKN1A、CDK6 and CCND2 were predicted by specific PPI networks.3.PSCI compared with NC group,a total of 27 DE-miRNA(P<0.05,|log2FC|≥1),including hsa-miR-548as-5P、hsa-miR-5186、hsa-miR-147 a etc.Target genes enriched in cellular senescence、p53 and tight junction signal pathways.Seven key genes AR、CDK2、CCND1、BMI1、CDK6、CCNB1 and NPM1 were predicted by specific PPI networks.4.PSCI group compared with PSNCI group,were identified 22 DE-miRNA(P<0.05,|log2FC|≥1),Such as hsa-miR-449b-5p、hsa-miR-5582-3p、hsa-miR-5186、hsa-miR-548ak、hsa-miR-147a、hsa-miR-8485 etc.Target genes enriched in cell cycle,cellular senescence and Fox O/p53/AMPK signaling pathways.Ten key genes BMI1、CDK2、CCNB1、KRAS、CCND1、CDK6、MYCN、AR、E2F3 and GSK3 B were predicted by specific PPI networks.Conclusions:1.In combination with high throughput sequencing and signaling analysis,our study found that:(1)hsa-miR-4655-5、hsa-miR-4478、hsa-miR-548as-5p、hsa-miR-5186、hsa-miR-187-5p、hsa-miR-3157-5p and hsa-miR-519c-3p are expected to be potential biological targets for the diagnosis and treatment of AD,participating in the occurrence of AD through ATM、MYC、PTEN and other genes acting on Fox O、MAPK and other pathways;(2)hsa-miR-6883-5p、hsa-miR-449b-5p、hsa-miR-686868-3p are expected to be biomarkers for the differential diagnosis of AD and PSCI,participate in the occurrence of AD through the action of CDKN1A、CDK6 and CCND2 on p53 and Hippo signaling pathways;(3)hsa-miR-548as-5p、hsa-miR-5186、and hsa-miR-147 a are expected to be potential biological targets for the diagnosis and treatment of PSCI,participate in the occurrence of PSCI through the action of AR、CDK2、CCND1、BMI1 on cellular senescence and p53 signaling pathways;(4)hsa-miR-449b-5p、hsa-miR-5582-3p、hsa-miR-5186、hsa-miR-548ak、hsa-miR-147a、and hsa-miR-885 are expected to be biomarkers for the differential diagnosis of PSCI and PSNCI,participate in the occurrence of PSCI through the action of BMI1、CDK2、CCNB1 on Fox O/p53/AMPK signaling pathways;2.The enrichment analysis and specific PPI network analysis provide a new experimental basis and theoretical basis for future studies on the pathogenesis of AD and PSCI.