Elevated miRNA Inversely Correlates with E-cadherin Gene Expression in Tissue Biopsies from Crohn Disease Patients in contrast to Ulcerative Colitis Patients

Abstract

Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn disease (CD). Similar symptoms, but different treatment procedures for both diseases require precise diagnosis. MicroRNAs (miRNAs) are major posttranscriptional players that regulate the expression of genes during the inflammation and thus could be appropriate biomarkers for differentiation between UC and CD. For this purpose, we analyzed the expression of miR-21-3p, miR-31-3p, miR-125b-1-3p, miR-146a-3p, miR-155-5p, and E-cadherin (CDH1) genes associated with IBD, in 67 tissue samples: 28 inflamed mucosa samples (n=16 UC, n=12 CD), 28 adjacent normal colonic mucosa (n=16 UC, n=12 CD), and 11 normal mucosa from healthy patients using reverse transcription real-time RT-PCR. We found all analyzed miRNAs were significantly overexpressed in UC tissue as compared to adjacent normal tissue of patients with UC, as well as to normal mucosa from healthy controls. Four miRNAs (except miR-125b-1-3p) were significantly upregulated in CD lesions as compared to adjacent normal tissue of patients with CD, and four miRNAs, except miR-146a-3p, were significantly higher in CD samples compared to normal mucosa from healthy individuals. In the CD group, we found an inverse correlation between miR-155-5p or miR-146a-3p expressions and CDH1expression in inflamed mucosa. This type of correlation was also detected for miR-213p in adjacent normal tissue and CDH1 in inflamed mucosa, as well as between miR-155-5p and CDH1 in adjacent normal tissue. Elevated miRNA expression is characteristic for IBD-mediated inflammation process and inversely correlated with CDH1 gene expression, which suggest involvement of epithelial to mesenchymal transition (EMT) in IBD development.

New Metabolic and Genetic Biomarkers for Diagnosis of Ulcerative Colitis

“…Also downregulated CDH1 was negatively correlated with miR-155-5p expression in both the inflamed mucosa and adjacent mucosa of such patients, which can assume that this expression pattern may differentiate CD from UC. By comparing UC tissue to adjacent normal tissue but alo to normal mucosa from healthy controls, all analyzed miRNAs in this study were significantly overexpressed in UC tissue, with some limitations in differentiating UC and CD [3]. In addition, Mohammadi et al identified a panel of ten miRNAs differentially expressed in CD patients in endoscopic remission compared to healthy control subjects, miR-874-3p making the difference between the UC and CD cases.…”

“…Inflammatory bowel diseases (IBD) consist of two major clinical phenotypes: ulcerative colitis (UC) and Crohn's disease (CD) [1]. Europe has the highest incidence of IBD, with 2.5-3 million people affected [2], while in North America there are 1.5 million people with IBD [3].…”

The Impact of MicroRNAs during Inflammatory Bowel Disease: Effects on the Mucus Layer and Intercellular Junctions for Gut Permeability

“…An overview of miRNA influence on adherens junction regulation can be seen in Figure 2 and further summarized in Table 2. A negative correlation between levels of E-cadherin and miR-21 was found in UC patients; exosome-derived miR-21a-5p from abnormally polarised macrophages decreased levels of E-cadherin in the epithelium, exacerbating DSS-induced colitis in mice [195][196][197] miR-130a-3p…”

LINC01272 Activates Epithelial-Mesenchymal Transition Through miR-153-5p in Crohn’s Disease

“…EMT has a dual effect on the formation of tissue brosis: (1) EMT increases the number of mesenchymal cells and matrix production; (2) EMT causes the loss of epithelial cells and increases tissue damage 13,14 . During this process, the expression of epithelial cell markers such as E-cadherin were decreased, and the expression of mesenchymal cell markers such as smooth muscle agonist protein (α-SMA), N-cadherin (N cadherin), and bronectin increase [15][16][17][18] .…”