The Construction and Comprehensive Analysis of Inflammation-Related ceRNA Networks and Tissue-Infiltrating Immune Cells in Ulcerative Progression.

Jia-Wei Lu,Wei-Li Liu,Li-Hong Teng,Aimaier Rouzigu,Shibiao Wan

doi:10.1155/2021/6633442

Abstract

Ulcerative colitis (UC) is a common disease with great variability in severity, with a high recurrence rate and heavy disease burden. In recent years, the different biological functions of competing endogenous RNA (ceRNA) networks of long noncoding RNAs (lncRNAs) and microRNAs (miRs) have aroused wide concerns, the ceRNA network of ulcerative colitis (UC) may have potential research value, and these expressed noncoding RNAs may be involved in the molecular basis of inflammation recurrence and progression. This study analyzed 490 colon samples associated with UC from 4 gene expression microarrays from the GEO database and identified gene modules by weighted correlation network analysis (WGCNA). CIBERSORT detected tissue-infiltrating leukocyte profiling by deconvolution of microarray data. LncBase and multiMIR were used to identify lncRNA-miRNA-mRNA interaction. We constructed a ceRNA network which includes 4 lncRNAs (SH3BP5-AS1, MIR4435-2HG, ENTPD1-AS1, and AC007750.1), 5 miRNAs (miR-141-3p, miR-191-5p, miR-192-5p, miR-194-5p, and miR196-5p), and 52 mRNAs. Those genes are involved in interleukin family signals, neutrophil degranulation, adaptive immunity, and cell adhesion pathways. lncRNA MIR4435-2HG is a variable in the decision tree for moderate-to-severe UC diagnostic prediction. Our work identifies potential regulated inflammation-related lncRNA-miRNA-mRNA regulatory axes. The regulatory axes are dysregulated during the deterioration of UC, suggesting that it is a risk factor for UC progression.

Highlights

Ulcerative colitis (UC) is a chronic and incurable inflammatory disease, which most often affects the gastrointestinal tract
The Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) database was searched for publicly available studies and samples that fulfilled the following criteria for analysis: [1] the species of the samples was Homo sapiens, [2] the gene expression data series contained UC colon tissue and normal colon tissue samples, [3] the selected dataset should be over 15 samples, and [4] the characteristic of samples from a gene expression study contained UC activity assessment
We noticed that turquoise modules were positively related to the severity of ulcerative colitis among four datasets (Figure 1(c)), green, blue, and tan modules were negatively related to the development of ulcerative colitis among four datasets (Figure 1(c)), and the bar plots revealed that the eigengene value of modules correlated with the disease severity (Figure 1(d))

Summary

Introduction

Ulcerative colitis (UC) is a chronic and incurable inflammatory disease, which most often affects the gastrointestinal tract. A recent study reported that UC prevalence is increasing rapidly worldwide with a high recurrence rate and heavy disease burden [1]. Patients with UC need a lifelong course of drugs, which results in high psychological and financial burdens to patients. It is urgent to deepen the understanding of the pathogenesis of ulcerative colitis progression at the molecular level to determine new therapeutic and disease surveillance strategies. The gene expression network of the disease has been predicted to be sophisticated and fathomable, involving a large variety of characters, such as transcription factors (TFs), microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and protein-coding genes (mRNAs)

Methods

Results

Discussion

Conclusion