Dataset Information

Constructing a ceRNA-immunoregulatory network associated with the development and prognosis of human atherosclerosis through weighted gene co-expression network analysis.

ABSTRACT: There is now overwhelming experimental and clinical evidence that atherosclerosis (AS) is a chronic inflammatory disease. The recent discovery of a new group of mediators known as competing endogenous RNA (ceRNA) offers a unique opportunity for investigating immunoregulation in AS. In this study, we used gene expression profiles from GEO database to construct a lncRNA-miRNA-mRNA ceRNA network during AS plaque development through weighted gene co-expression network analysis (WGCNA). GO annotation and pathway enrichment analysis suggested that the ceRNA network was mainly involved in the immune response. CIBERSORT and GSVA were used to calculate the immune cell infiltration score and identified macrophage as hub immunocyte in plaque development. A macrophage related ceRNA subnetwork was constructed through correlation analysis. Samples from Biobank of Karolinska Endarterectomy (BiKE) were used to identify prognostic factors from the subnetwork and yielded 7 hub factors that can predict ischemic events including macrophage GSVA score and expression value of AL138756.1, CTSB, MAFB, LYN, GRK3, and BID. A nomogram based on the key factors was established. GSEA identified that the PD1 signaling pathway was negatively associated with these prognostic factors which may explain the cardiovascular side effect of immune checkpoint therapy in anti-tumor treatment.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7880393 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Constructing a ceRNA-immunoregulatory network associated with the development and prognosis of human atherosclerosis through weighted gene co-expression network analysis.

Liu Yaozhong Y Liu Na N Liu Qiming Q

Aging 20210117 2

There is now overwhelming experimental and clinical evidence that atherosclerosis (AS) is a chronic inflammatory disease. The recent discovery of a new group of mediators known as competing endogenous RNA (ceRNA) offers a unique opportunity for investigating immunoregulation in AS. In this study, we used gene expression profiles from GEO database to construct a lncRNA-miRNA-mRNA ceRNA network during AS plaque development through weighted gene co-expression network analysis (WGCNA). GO annotation ...[more]

PMID: 33460396

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Project description:BackgroundPatients with ulcerative colitis are at an increased risk of developing colorectal cancer with a prolonged disease course. Many studies have shown that alterations in the immune microenvironment play a key role in ulcerative colitis-associated colorectal cancer. Additionally, competing endogenous RNAs have important functions in immunoregulation, affecting inflammation and tumorigenesis. However, the complexity and behavioral characteristics of the competing endogenous RNA immunoregulatory network in ulcerative colitis-associated colorectal cancer remain unclear. We constructed a competing endogenous RNA immunoregulatory network to discover and validate a novel competing endogenous RNA immunoregulatory axis to provide insight into ulcerative colitis-associated colorectal cancer progression.MethodsThe competing endogenous RNA immunoregulatory network was constructed using differential expression analysis, weighted gene co-expression network analysis, and immune-related genes. Cmap was used to identify small-molecule drugs with therapeutic potential in ulcerative colitis-associated colorectal cancer. The ulcerative colitis-associated colorectal cancer-related pathways were identified by gene set variation and enrichment analysis. CIBERSORT, single-sample Gene Set Enrichment Analysis, and xCell were used to evaluate the infiltration of immune cells and screen hub immunocytes. The competing endogenous RNA immunoregulatory axis was identified by correlation analysis.ResultsWe identified 130 hub immune genes and constructed a competing endogenous RNA immunoregulatory network consisting of 56 long non-coding RNAs, four microRNAs, and six targeted hub immune genes. Four small-molecule drugs exerted potential therapeutic effects by reversing the expression of hub immune genes. Pathway analysis showed that the NF-κB pathway was significantly enriched. Neutrophils were identified as hub immunocytes, and IL6ST was significantly positively correlated with the neutrophil count. In addition, NEAT1 may serve as a competing endogenous RNA to sponge miR-1-3p and promote IL6ST expression.ConclusionsThe competing endogenous RNA immunoregulatory axis may regulate neutrophil infiltration, affecting the occurrence of ulcerative colitis-associated colorectal cancer.

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Dataset Information

Constructing a ceRNA-immunoregulatory network associated with the development and prognosis of human atherosclerosis through weighted gene co-expression network analysis.

Publications

Constructing a ceRNA-immunoregulatory network associated with the development and prognosis of human atherosclerosis through weighted gene co-expression network analysis.

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