人类 microRNA-4433 (hsa-miR-4443) 靶向 18 个基因，成为神经退行性疾病的风险因素。

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

机构信息

Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.

School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.

出版信息

Curr Alzheimer Res. 2022;19(7):511-522. doi: 10.2174/1567205019666220805120303.

DOI:10.2174/1567205019666220805120303

PMID:35929619

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9906632/

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.

摘要

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），是导致老年人发病率、死亡率和认知障碍的常见原因。

目的

我们旨在了解神经退行性疾病皮质的转录组特征，并深入了解差异表达 microRNAs 在神经退行性疾病发生和发展中的靶基因。

方法

使用 R 软件的 Limma 包分析 GSE33000、GSE157239、GSE64977 和 GSE72962 数据集，以鉴定神经退行性疾病皮质中的差异表达基因（DEGs）和 microRNAs。GO 富集分析、KEGG 富集分析和基因互作网络分析等生物信息学方法用于探索 DEGs 的生物学功能。加权基因共表达网络分析（WGCNA）用于将 DEGs 聚类成模块。使用 RNA22、miRDB、miRNet 2.0 和 TargetScan7 数据库预测 microRNAs 的靶基因。

结果

在 310 名阿尔茨海默病（AD）患者、157 名亨廷顿病（HD）患者和 157 名非痴呆对照（Con）个体中，鉴定出 214 个共同 DEGs。这些共同 DEGs 被过滤成 2 个不同的相互作用网络复合物，代表免疫相关基因和突触相关基因。WGCNA 结果鉴定出 5 个模块：黄色、蓝色、绿色、绿松石色和棕色。大多数共同 DEGs 聚类到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，在神经退行性疾病皮质中，唯一共同上调的 microRNA 是靶向 18 个共同 DEGs 的人类 microRNA-4433（hsa-miR-4443）。