Construction of a ceRNA immunoregulatory network related to the development of vascular dementia through a weighted gene coexpression network analysis

Abstract

Background: To date, vascular dementia (VaD) lacks effective treatment in clinical practice. There is also growing evidence that VaD may be closely related to the immune response. The development of highthroughput technology, and the recently discovered group of new mediators called competitive endogenous RNAs (ceRNA), provides a unique opportunity to study the immunomodulation of VaD.Methods: In this study, we used gene expression profiles in the Gene Expression Omnibus (GEO) database to obtain immune-related gene coexpression modules through a weighted gene coexpression network analysis (WGCNA) and gene enrichment analysis. We extracted and merged long non-coding RNA (lncRNA) and microRNA (miRNA) expressions from the GEO database and mapped them with related databases.Subsequently, we used Cytoscape to construct a lncRNA-miRNA-mRNA network, and then we performed an enrichment analysis on the mRNAs in the network to determine their regulatory function. Subsequently, we used an ImmuCellAI immune infiltration analysis and constructed a ceRNA sub-network of related immune cells. Finally, we conducted a gene set enrichment analysis (GSEA) to determine the potential regulatory pathways of the key factors.Results: As a result, we identified the blue module as the key module of immunity and constructed the related CeRNA network. Immune infiltration analysis showed that natural killer T (NKT) cells may be the key immune cells of VaD. Using a Pearson correlation analysis, we identified that B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1 may be the key factors of VaD. Our subsequent GSEA analysis showed that lncRNA NEAT1 may be regulated by NK cells and toll-like receptors.Conclusions: Our research provides new therapeutic targets for vascular dementia from the immunological perspective for the first time, including B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1, and our research hopes to provide new treatment options for VaD.

Quality of the Evidence Supporting the Role of Acupuncture Interventions for Vascular Dementia

“… 2 As the second most common type of dementia, after Alzheimer’s disease, VaD afflicts nearly 46.8 million individuals around the world. In Europe and North America, VaD accounts for about 15% to 20% of people with dementia, while in developing countries this proportion has risen to approximately 30%, 3 and cases are expected to increase as the population ages. 4 , 5 Besides vascular problems, risk factors such as smoking, age, alcoholism, and diabetes should not be ignored.…”