Human microRNA-4433 (hsa-miR-4443) Targets 18 Genes to be a Risk Factor of Neurodegenerative Diseases.

IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Current Alzheimer research Pub Date : 2022-01-01 DOI:10.2174/1567205019666220805120303
Xing Ge, Tingting Yao, Chaoran Zhang, Qingqing Wang, Xuxu Wang, Li-Chun Xu
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引用次数: 3

Abstract

Background: Neurodegenerative diseases, such as Alzheimer's disease patients (AD), Huntington's disease (HD) and Parkinson's disease (PD), are common causes of morbidity, mortality, and cognitive impairment in older adults.

Objective: We aimed to understand the transcriptome characteristics of the cortex of neurodegenerative diseases and to provide an insight into the target genes of differently expressed microRNAs in the occurrence and development of neurodegenerative diseases.

Methods: The Limma package of R software was used to analyze GSE33000, GSE157239, GSE64977 and GSE72962 datasets to identify the differentially expressed genes (DEGs) and microRNAs in the cortex of neurodegenerative diseases. Bioinformatics methods, such as GO enrichment analysis, KEGG enrichment analysis and gene interaction network analysis, were used to explore the biological functions of DEGs. Weighted gene co-expression network analysis (WGCNA) was used to cluster DEGs into modules. RNA22, miRDB, miRNet 2.0 and TargetScan7 databases were performed to predict the target genes of microRNAs.

Results: Among 310 Alzheimer's disease (AD) patients, 157 Huntington's disease (HD) patients and 157 non-demented control (Con) individuals, 214 co-DEGs were identified. Those co-DEGs were filtered into 2 different interaction network complexes, representing immune-related genes and synapserelated genes. The WGCNA results identified five modules: yellow, blue, green, turquoise, and brown. Most of the co-DEGs were clustered into the turquoise module and blue module, which respectively regulated synapse-related function and immune-related function. In addition, human microRNA-4433 (hsa-miR-4443), which targets 18 co-DEGs, was the only 1 co-up-regulated microRNA identified in the cortex of neurodegenerative diseases.

Conclusion: 214 DEGs and 5 modules regulate the immune-related and synapse-related function of the cortex in neurodegenerative diseases. Hsa-miR-4443 targets 18 co-DEGs and may be a potential molecular mechanism in neurodegenerative diseases' occurrence and development.

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人microRNA-4433 (hsa-miR-4443)靶向18个基因成为神经退行性疾病的危险因素
背景:神经退行性疾病,如阿尔茨海默病(AD)、亨廷顿病(HD)和帕金森病(PD),是老年人发病率、死亡率和认知障碍的常见原因。目的:了解神经退行性疾病皮层的转录组特征,揭示不同表达的microrna在神经退行性疾病发生发展中的靶基因。方法:采用R软件Limma软件包对GSE33000、GSE157239、GSE64977和GSE72962数据集进行分析,鉴定神经退行性疾病的皮质差异表达基因(DEGs)和microrna。利用生物信息学方法,如GO富集分析、KEGG富集分析和基因相互作用网络分析,探索DEGs的生物学功能。加权基因共表达网络分析(加权基因共表达网络分析,WGCNA)将基因序列聚类成模块。使用RNA22、miRDB、miRNet 2.0和TargetScan7数据库预测microrna的靶基因。结果:在310例阿尔茨海默病(AD)患者、157例亨廷顿病(HD)患者和157例非痴呆对照(Con)中,发现214例共deg。这些共deg被过滤成2种不同的相互作用网络复合物,分别代表免疫相关基因和突触相关基因。WGCNA的结果确定了五个模块:黄色、蓝色、绿色、绿松石色和棕色。大部分co- deg聚集在绿松石模块和蓝色模块中,分别调节突触相关功能和免疫相关功能。此外,人类microRNA-4433 (hsa-miR-4443)靶向18个共degs,是唯一在神经退行性疾病皮层中发现的1个共上调的microRNA。结论:214个DEGs和5个模块调节神经退行性疾病中皮层的免疫相关和突触相关功能。Hsa-miR-4443靶向18个共degs,可能是神经退行性疾病发生发展的潜在分子机制。
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来源期刊
Current Alzheimer research
Current Alzheimer research 医学-神经科学
CiteScore
4.00
自引率
4.80%
发文量
64
审稿时长
4-8 weeks
期刊介绍: Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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