The Role of MicroRNAs upon Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease

Boros, Éva; Nagy, István

doi:10.3390/cells8111461

Cited by 18 publications

(22 citation statements)

References 166 publications

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“…This process is associated with the formation of intestinal fibrosis and may play a role in the development of IBD-related colorectal cancer [20]. We have previously reported that the expression of EMT activating genes significantly increased both in the inflamed colon samples of TNBS treated rats as well as in IBD patients [13,15,19]. In addition, the expression of growth factors (EGR1, FGF2 and FGF7), signal transducer molecules (JAK2, NOTCH2 and HIF1α), EMT inducing transcriptional factors (ZEB2, SNAI1), extracellular matrix remodeler MMP9 and mesenchymal markers (LOX and VIM) are all upregulated in the inflamed colon tissues, while the expression of the epithelial marker CDH1 decreased [13,15,19].…”

Section: Correlation Between Murine and Human Samplesmentioning

confidence: 99%

“…To validate our transcriptome data, first we compared the RNA-Seq results to our previous data on gene expression changes related to epithelial-to-mesenchymal transition (EMT) [13,15,19]. Upon EMT, epithelial cells lose their epithelial characteristics, their cell-cell connections disintegrate and cell motility enhances.…”

Section: Correlation Between Murine and Human Samplesmentioning

confidence: 99%

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Transcriptome Based Profiling of the Immune Cell Gene Signature in Rat Experimental Colitis and Human IBD Tissue Samples

et al. 2020

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Chronic intestinal inflammation is characteristic of Inflammatory Bowel Disease (IBD) that is associated with the exaggerated infiltration of immune cells. A complex interplay of inflammatory mediators and different cell types in the colon are responsible for the maintenance of tissue homeostasis and affect pathological conditions. Gene expression alteration of colon biopsies from IBD patients and an in vivo rat model of colitis were examined by RNA-Seq and QPCR, while we used in silico methods, such as Ingenuity Pathway Analysis (IPA) application and the Immune Gene Signature (ImSig) package of R, to interpret whole transcriptome data and estimate immune cell composition of colon tissues. Transcriptome profiling of in vivo colitis model revealed the most significant activation of signaling pathways responsible for leukocyte recruitment and diapedesis. We observed significant alteration of genes related to glycosylation or sensing of danger signals and pro- and anti-inflammatory cytokines and chemokines, as well as adhesion molecules. We observed the elevated expression of genes that implies the accumulation of monocytes, macrophages, neutrophils and B cells in the inflamed colon tissue. In contrast, the rate of T-cells slightly decreased in the inflamed regions. Interestingly, natural killer and plasma cells do not show enrichment upon colon inflammation. In general, whole transcriptome analysis of the in vivo experimental model of colitis with subsequent bioinformatics analysis provided a better understanding of the dynamic changes in the colon tissue of IBD patients.

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Section: Correlation Between Murine and Human Samplesmentioning

confidence: 99%

Section: Correlation Between Murine and Human Samplesmentioning

confidence: 99%

Transcriptome Based Profiling of the Immune Cell Gene Signature in Rat Experimental Colitis and Human IBD Tissue Samples

et al. 2020

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“…miRNAs have a huge potential as biological markers, because there are key molecular players in regulating a multitude of cellular processes, including IBD development [23,24]. Specific miRNA signatures have been observed in IBD, associated with canonical signaling pathways regulating autophagy, inflammation, fibrosis, or EMT [25]. One of the analyzed miRNAs in the present paper is miR-155 which was shown to inhibit the suppressor of cytokine signaling (SOCS1)-a negative regulator of the Janus kinase/signal transducers and activators of transcription (JAK/STAT signaling); thus, elevating the expression of miR-155 could enhance inflammation in the intestine of IBD patients by immune system perturbation [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…Specific miRNA signatures have been observed in IBD, associated with canonical signaling pathways regulating autophagy, inflammation, fibrosis, or EMT [25]. One of the analyzed miRNAs in the present paper is miR-155 which was shown to inhibit the suppressor of cytokine signaling (SOCS1)-a negative regulator of the Janus kinase/signal transducers and activators of transcription (JAK/STAT signaling); thus, elevating the expression of miR-155 could enhance inflammation in the intestine of IBD patients by immune system perturbation [25,26]. In our study, we noticed an increased expression of miR-155-5p in both inflamed tissue and, most important, also adjacent tissue of patients with CD, suggesting that elevated miR-155-5p expression contributes to CD development.…”

Section: Discussionmentioning

confidence: 99%

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

Guz

Dworzański

Jeleniewicz

et al. 2020

BioMed Research International

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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.

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“…Physiologically, EMT can be observed during embryogenesis, tissue development and wound healing [48]. It is also a common phenomenon during carcinogenesis and can either induce or coexist with various malignancies such as breast cancer, thyroid cancer, cholangiocarcinoma, non-small cell lung carcinoma, colorectal cancer, inflammatory bowel disease or GC [49][50][51][52][53][54][55][56][57][58][59][60]. During the EMT process, ECs undergo a series of biochemical reactions that eventually lead to alterations in the cells' morphology, especially the loss of the polarity of cells [17,61].…”

Section: Figurementioning

confidence: 99%

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

Baj

Brzozowska

Forma

et al. 2020

IJMS

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Infection with Helicobacter pylori, a Gram-negative, microaerophilic pathogen often results in gastric cancer in a subset of affected individuals. This explains why H. pylori is the only bacterium classified as a class I carcinogen by the World Health Organization. Several studies have pinpointed mechanisms by which H. pylori alters signaling pathways in the host cell to cause diseases. In this article, the authors have reviewed 234 studies conducted over a span of 18 years (2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020). The studies investigated the various mechanisms associated with gastric cancer induction. For the past 1.5 years, researchers have discovered new mechanisms contributing to gastric cancer linked to H. pylori etiology. Alongside alteration of the host signaling pathways using oncogenic CagA pathways, H. pylori induce DNA damage in the host and alter the methylation of DNA as a means of perturbing downstream signaling. Also, with H. pylori, several pathways in the host cell are activated, resulting in epithelial-to-mesenchymal transition (EMT), together with the induction of cell proliferation and survival. Studies have shown that H. pylori enhances gastric carcinogenesis via a multifactorial approach. What is intriguing is that most of the targeted mechanisms and pathways appear common with various forms of cancer.EMT refers to the process by which the mesenchymal phenotype is acquired by epithelial cells (ECs) mainly via the reduction of their intracellular adhesions and proliferative capacity (Figure 1.) [47].

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The Role of MicroRNAs upon Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease

Cited by 18 publications

References 166 publications

Transcriptome Based Profiling of the Immune Cell Gene Signature in Rat Experimental Colitis and Human IBD Tissue Samples

Transcriptome Based Profiling of the Immune Cell Gene Signature in Rat Experimental Colitis and Human IBD Tissue Samples

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

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

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