Role of Altered Expression of miR-146a, miR-155, and miR-122 in Pediatric Patients with Inflammatory Bowel Disease

Béres, Nóra; Szabó, Dolóresz; Kocsis, Dorottya; Szűcs, Dániel; Kiss, Zoltán; Müller, Katalin Eszter; Lendvai, Gábor; Kiss, András; Arató, András; Sziksz, Erna; Vannay, Ádám; Szabó, Attila; Veres, Gábor

doi:10.1097/mib.0000000000000687

Cited by 70 publications

(52 citation statements)

References 74 publications

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“…Among the commonly deregulated miRNAs, microRNA-375 was previously described as being up-regulated in serum from UC and CD patients 49 and in IL10 −/− mice 50 . Micro-RNA-122 is known to be increased in several inflammatory conditions 51, 52 , and was recently observed to be increased in uninvolved colonic mucosa of pediatric CD patients 53 and in colon biopsies during the progression from non-neoplasia to dysplasia in a group of 4 CD patients 54 , and downregulated in transition from dysplasia to cancer in this same group 54 . Finally, miRNA-150 was previously shown to be up-regulated in colonic tissues of DSS-induced colitic mice and UC patients 55 .…”

Section: Discussionmentioning

confidence: 88%

Serum miRNA signature diagnoses and discriminates murine colitis subtypes and predicts ulcerative colitis in humans

Viennois

Zhao

Han

et al. 2017

Sci Rep

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Inflammatory bowel disease (IBD) is difficult to diagnose due to nonspecific and variable symptoms, and lack of reliable diagnostic tests. Current methods are invasive, non-sensitive, non-predictive, and do not easily discriminate between its two main forms. Consequently, there remains a great need for reliable serum markers for IBD. Here, using a longitudinal study of various mouse models of colitis, we identified a serum miRNA signature that indicated the development of colitis and discriminated between inflammations of various origins (colitis from arthritis). Unlike the existing biomarkers, the newly identified signature also serves to distinguish individuals at risk, predict the type of inflammation, and evaluate the response to therapeutics. Moreover, the miRNA signature identified in mice predicted ulcerative colitis with 83.3% accuracy. In future, the signature identified herein could play a central role in monitoring inflammatory disorders and therapeutic responses in patients, thereby paving the way for personalized medicine.

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Section: Discussionmentioning

confidence: 88%

Serum miRNA signature diagnoses and discriminates murine colitis subtypes and predicts ulcerative colitis in humans

Viennois

Zhao

Han

et al. 2017

Sci Rep

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“…Moreover, upregulation of miR‐146b‐5p is associated with cell proliferation, aggressiveness, and poor prognosis as an oncogene in papillary thyroid carcinoma, lung cancer, and gastrointestinal malignant tumour . In IBD, miR‐146a expression was elevated in the colonic mucosa of both paediatric and adult patients compared to in healthy controls . Peck et al also found that miR‐146b‐5p was upregulated in colonic RNA‐sequencing data of patients with CD and in healthy controls.…”

Section: Discussionmentioning

confidence: 98%

Circulating microRNA146b‐5p is superior to C‐reactive protein as a novel biomarker for monitoring inflammatory bowel disease

Chen

Liu

et al. 2019

Aliment Pharmacol Ther

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Background:Owing to the importance of early treatment, simple and reliable methods for monitoring inflammatory bowel disease (IBD) are needed. Aims:To determine whether circulating microRNAs are reliable biomarkers for IBD monitoring.Methods: Serum levels of 17 candidate microRNAs were measured by quantitative real-time polymerase chain reaction in a discovery cohort (n = 120). Differentially expressed serum microRNAs were further investigated in an independent training cohort (n = 341). Correlations between relative microRNA levels and disease activity were evaluated. A disease control group was included to investigate the specificity of microRNA. Logistical regression was used to construct a microRNA classifier to identify endoscopic activity. Its predictive value was explored in the validation cohort (n = 66) using the area under the receiver operating characteristic curve (AUC).Results: Serum microRNA146b-5p (miR-146b-5p) expression was 2.87-and 2.72fold higher in patients with Crohn's disease and ulcerative colitis, respectively, than in healthy controls. Serum miR-146b-5p was significantly correlated with disease activity and was more specific than C-reactive protein (CRP). A classifier was built for Crohn's disease, ie P [Endoscopically active] = 1 1 þ e 2:937À0:737ðmiRÀ146bÀ5pÞÀ0:008PLT , with a greater AUC of 0.869 [0.764-0.940] than that for CRP (0.680 [0.554-0.790]) (P = 0.0043). Conclusions:MiR-146b-5p may better reflect mucosal inflammation in IBD than CRP. The Crohn's disease classifier developed in this study may be valuable for identifying endoscopic activity in patients with Crohn's disease.

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“…Given the potential relationship between FOXP3 and miR-31 ( Figure 5), it is unsurprising to find that miR-31 is dysregulated in several autoimmune diseases such as IBD or Crohn's disease 85,86 and Kawasaki disease. 87 Therefore, understanding the molecular mechanisms by which FOXP3 and miR-31 regulate each other, and identifying the target genes within this regulatory network, could contribute to the development of novel treatments for autoimmune disease.…”

Section: Foxp3 Cooperates With Micrornas Via Regulatory Loops Which Tmentioning

confidence: 99%

Unravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease

et al. 2018

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Regulatory T cells (Treg) are critical for preventing autoimmunity and curtailing responses of conventional effector T cells (Tconv). The reprogramming of T‐cell fate and function to generate Treg requires switching on and off of key gene regulatory networks, which may be initiated by a subtle shift in expression levels of specific genes. This can be achieved by intermediary regulatory processes that include microRNA and long noncoding RNA‐based regulation of gene expression. There are well‐documented microRNA profiles in Treg and Tconv, and these can operate to either reinforce or reduce expression of a specific set of target genes, including FOXP3 itself. This type of feedforward/feedback regulatory loop is normally stable in the steady state, but can alter in response to local cues or genetic risk. This may go some way to explaining T‐cell plasticity. In addition, in chronic inflammation or autoimmunity, altered Treg/Tconv function may be influenced by changes in enhancer–promoter interactions, which are highly cell type‐specific. These interactions are impacted by genetic risk based on genome‐wide association studies and may cause subtle alterations to the gene regulatory networks controlled by or controlling FOXP3 and its target genes. Recent insights into the 3D organisation of chromatin and the mapping of noncoding regulatory regions to the genes they control are shedding new light on the direct impact of genetic risk on T‐cell function and susceptibility to inflammatory and autoimmune conditions.

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Role of Altered Expression of miR-146a, miR-155, and miR-122 in Pediatric Patients with Inflammatory Bowel Disease

Abstract: Our results showed altered expression of miR-146a, -155, and -122 in the colonic mucosa of children with IBD and in TNF-α-treated colonic epithelial cells. Our data suggest the TNF-α-related involvement of these miRs in the pathogenesis of IBD.

Cited by 70 publications

References 74 publications

Serum miRNA signature diagnoses and discriminates murine colitis subtypes and predicts ulcerative colitis in humans

Serum miRNA signature diagnoses and discriminates murine colitis subtypes and predicts ulcerative colitis in humans

Circulating microRNA146b‐5p is superior to C‐reactive protein as a novel biomarker for monitoring inflammatory bowel disease

Unravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease

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