Low Serum Levels of MicroRNA-19 Are Associated with a Stricturing Crohnʼs Disease Phenotype

PurposeThe aim of the present study was to assess the expression of miRNAs in the Vitreous Humor (VH) of patients with Macular Hole (MH) and Epiretinal Membrane (ERM) compared to a control group.MethodsIn this prospective, comparative study, 2-ml of VH was extracted from the core of the vitreous chamber in consecutive patients who underwent standard vitrectomy for ERM and MH. RNA was extracted and TaqMan® Low Density Arrays (TLDAs) were used to profile the transcriptome of 754 miRNAs. Results were validated by single TaqMan® assays. Finally, we created a biological network of differentially expressed miRNA targets and their nearest neighbors.ResultsOverall 10 eyes with MH, 16 eyes with idiopathic ERM and 6 controls were enrolled in the study. Profiling data identified 5 miRNAs differentially expressed in patients affected by MH and ERM with respect to controls. Four were downregulated (miR-19b, miR-24, miR-155, miR-451) and 1 was downregulated (miR-29a); TaqMan® assays of the VH of patients affected by MH and ERM, with respect to controls, showed that the most differentially expressed were miR-19b (FC -9.13, p:<0.00004), mir-24 (FC -7.52, p:<0.004) and miR-142-3p (FC -5.32, p:<0.011). Our network data showed that deregulation of differentially expressed miRNAs induces an alteration of several pathways associated with genes involved in both MH and ERM.ConclusionThe present study suggests that disregulation of miR-19b, miR-24 and miR-142-3p, might be related to the alterations that characterize patients affected by MH and ERM.

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“…In addition, its decreased serum level has been reported in association with intestinal fibrosis [36]. …”

Section: Discussionmentioning

confidence: 99%

“…Increased serum levels of miR-142-3p were associated with the presence and severity of scleroderma, an autoimmune disease that causes a progressive fibrotic tissue formation in the normal tissue architecture of various organs [36,43]. …”

Section: Discussionmentioning

confidence: 99%

miRNAs in the vitreous humor of patients affected by idiopathic epiretinal membrane and macular hole

et al. 2017

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“…Polytarchou and colleagues reported that serum miR-223-3p, miR-4454, miR23a-3p, and miR320e levels correlated with UC disease activity better than serum C-reactive protein levels [46]. Lewis et al identified miR-19a-3p and miR-19b-3p as markers of stricturing CD, both miRNAs were expressed at lower levels in the serum of CD patients with strictures in comparison to non-stricturing CD patients [39]. …”

Section: Circulating Mirna Expressionmentioning

confidence: 99%

MicroRNAs

Schaefer

2016

Current Opinion in Gastroenterology

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Purpose of review MicroRNAs (miRNAs), small noncoding RNA molecules of approximately 22 nucleotides, have emerged as critical mediators of gene expression. As the dysregulation of gene expression can have far reaching impact on health and disease, miRNAs are being examined as potent new mediators of disease as either biomarkers or potential therapeutic targets. The purpose of this review is to evaluate the contribution of miRNAs to inflammatory bowel disease (IBD) pathophysiology. Recent findings Recent studies have evaluated the expression of miRNAs in tissue and body fluid specimens from patients with of the main subtypes of IBD -Crohn’s disease (CD) and ulcerative colitis (UC). Unique miRNA expression patterns that may distinguish IBD subtypes have been uncovered. Summary Significant progress has been made in illuminating the complex interactive networks of miRNAs and gene targets in IBD. The potential use of miRNAs as disease biomarkers or therapeutics shows promise. However, there are still significant hurdles to overcome before miRNA-based therapeutics and diagnostics will be of clinical utility.

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“…20 MiR-19a-3p and miR-19b-3p are reduced in the serum of stricturing Crohn's disease patients compared with that of nonstricturing Crohn's disease. 21 Moreover, according to a multivariate analysis, the association between miR-19-3p and stricturing phenotype is independent of confounding clinical variables including ileal location and disease duration. 21 …”

Section: Mirsmentioning

confidence: 99%

“…21 Moreover, according to a multivariate analysis, the association between miR-19-3p and stricturing phenotype is independent of confounding clinical variables including ileal location and disease duration. 21 …”

Section: Mirsmentioning

confidence: 99%

Biomarkers of intestinal fibrosis – one step towards clinical trials for stricturing inflammatory bowel disease

Giuffrida

Pinzani

Corazza

et al. 2016

United European Gastroenterology Journal

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Intestinal fibrosis, caused by an excessive deposition of extracellular matrix components, and subsequent stricture development are a common complication of inflammatory bowel disease. However, currently there are no biomarkers which reliably predict the risk of developing intestinal strictures or identify early stages of fibrosis prior to clinical symptoms. Candidate biomarkers of intestinal fibrosis, including gene variants (i.e. nucleotide-binding oligomerization domain-2 gene), serum microRNAs (miR-19, miR-29), serum extracellular matrix proteins (i.e. collagen, fibronectin) or enzymes (i.e. tissue inhibitor of matrix metalloproteinase-1), serum growth factors (i.e. basic fibroblast growth factor, YKL-40), serum anti-microbial antibodies (i.e. anti-Saccharomyces cerevisiae) and circulating cells (i.e. fibrocytes) have shown conflicting results on relatively heterogeneous patients' cohorts, and none of them was proven to be strictly specific for fibrostenosis, but rather predictive of a disease disabling course. In this review we critically reassess the diagnostic and prognostic value of serum biomarkers of intestinal fibrosis in inflammatory bowel disease.

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Low Serum Levels of MicroRNA-19 Are Associated with a Stricturing Crohnʼs Disease Phenotype

Abstract: These data identify miR-19-3p as a potential circulating marker of stricturing CD. Our data show that microRNAs have utility as noninvasive biomarkers of stricturing CD. Further longitudinal studies are required to determine the prognostic value of miR-19-3p at diagnosis.

Cited by 56 publications

References 34 publications

miRNAs in the vitreous humor of patients affected by idiopathic epiretinal membrane and macular hole

miRNAs in the vitreous humor of patients affected by idiopathic epiretinal membrane and macular hole

MicroRNAs

Biomarkers of intestinal fibrosis – one step towards clinical trials for stricturing inflammatory bowel disease

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