A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease

Brest, Patrick; Lapaquette, Pierre; Souidi, Mouloud; Lebrigand, Kévin; Césaro, Annabelle; Vouret‐Craviari, Valérie; Mari, Bernard; Barbry, Pascal; Mosnier, Jean‐François; Hébuterne, Xavier; Harel‐Bellan, Annick; Mograbi, Baharia; Darfeuille‐Michaud, Arlette; Hofman, Paul

doi:10.1038/ng.762

Cited by 511 publications

(416 citation statements)

References 24 publications

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“…Apart from Atg16L1, other autophagy-related proteins such as IRGM [101][102][103] and NOD2 [104][105][106] are reported to be associated with Crohn's disease in humans [107]. However, since these proteins also play roles in biological processes other than autophagy, it remains unclear whether they relate to Crohn's disease via autophagy modulation.…”

Section: Crohn's Diseasementioning

confidence: 99%

Autophagy and human diseases

2013

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Autophagy is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation. Since the discovery of autophagy-related (Atg) genes in the 1990s, there has been a proliferation of studies on the physiological and pathological roles of autophagy in a variety of autophagy knockout models. However, direct evidence of the connections between ATG gene dysfunction and human diseases has emerged only recently. There are an increasing number of reports showing that mutations in the ATG genes were identified in various human diseases such as neurodegenerative diseases, infectious diseases, and cancers. Here, we review the major advances in identification of mutations or polymorphisms of the ATG genes in human diseases. Current autophagy-modulating compounds in clinical trials are also summarized.

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Section: Crohn's Diseasementioning

confidence: 99%

Autophagy and human diseases

2013

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“…Nguyen and colleagues [129] found that only miR7 was downregulated in eight active colonic CD patients compared to six healthy controls. In addition, miR206, miR424 [121] , miR106b [130] and miR196 [131] are also upregulated in active colonic CD. However, is there any tissuespecific miRNA expression profile in the gastrointestinal tract?…”

Section: Mirnas In CDmentioning

confidence: 99%

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

Zhang

2016

WJG

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Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn's disease. The pathogenesis of IBD is not fully understood as of yet. It is believed that IBD results from complicated interactions between environmental factors, genetic predisposition, and immune disorders. miRNAs are a class of small non-coding RNAs that can regulate gene expression by targeting the 3′-untranslated region of specific mRNAs for degradation or translational inhibition. miRNAs are considered to play crucial regulatory roles in many biologic processes, such as immune cellular differentiation, proliferation, and apoptosis, and maintenance of immune homeostasis. Recently, aberrant expression of miRNAs was revealed to play an important role in autoimmune diseases, including IBD. In this review, we discuss the current understanding of how miRNAs regulate autoimmunity and inflammation by affecting the differentiation, maturation, and function of various immune cells. In particular, we focus on describing specific miRNA expression profiles in tissues and peripheral blood that may be associated with the pathogenesis of IBD. In addition, we summarize the opportunities for utilizing miRNAs as new biomarkers and as potential therapeutic targets in IBD.

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“…It is generally believed that the mature miRNA then incorporates into the RNA-induced silencing complex, and guides this complex to the 3'-untranslated region (3'-UTR) of specific target mRNA transcripts to suppress translation or induce their degradation [1,2,[10][11][12][13] . However, miRNAbinding sites in coding regions as well as in the 5'-UTRs have also been reported [14][15][16][17][18][19] .…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have demonstrated miRNAs to be involved in inflammatory bowel disease (IBD) susceptibility, as polymorphisms in miRNA-binding sites affect the gene expression and thus seem to play a pivotal part in the pathogenesis of this chronic disorder [17,26] . Moreover, it has been found that miRNAs are differentially expressed in ulcerative colitis (UC) and Crohn's disease (CD) [27] , the two main forms of IBD.…”

Section: Introductionmentioning

confidence: 99%

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

Coskun¹

2013

WJG

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Author contributions: Coskun M and Bjerrum JT performed the experiments and data analysis, wrote the manuscript, and wrote the final revision of the article; Troelsen JT provided with analytical tools, intellectual input and advice; Olsen J provided with reagents and human tissue; Seidelin JB and Nielsen OH contributed to the conceptual design, drafting of the manuscript and revising it critically for important intellectual content; all authors approved the final submitted manuscript. Abstract AIM: To use microarray-based miRNA profiling of colonic mucosal biopsies from patients with ulcerative colitis (UC), Crohn's disease (CD), and controls in order to identify new potential miRNA biomarkers in inflammatory bowel disease. METHODS:Colonic mucosal pinch biopsies from the descending part were obtained endoscopically from patients with active UC or CD, quiescent UC or CD, as well as healthy controls. Total RNA was isolated and miRNA expression assessed using the miRNA microarray Geniom Biochip miRNA Homo sapiens (Febit GmbH, Heidelberg, Germany). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIM-CA-P+12 software package (Umetrics, Umea, Sweden). The microarray data were subsequently validated by quantitative real-time polymerase chain reaction (qPCR) performed on colonic tissue samples from active UC patients (n = 20), patients with quiescent UC (n = 19), and healthy controls (n = 20). The qPCR results were analyzed with Mann-Whitney U test. In silico prediction analysis were performed to identify potential miRNA target genes and the predicted miRNA targets were then compared with all UC associated susceptibility genes reported in the literature. RESULTS:The colonic mucosal miRNA transcriptome differs significantly between UC and controls, UC and CD, as well as between UC patients with mucosal inflammation and those without. However, no clear differences in the transcriptome of patients with CD and controls were found. The miRNAs with the strongest differential power were identified (miR-20b, miR-99a, miR-203, miR-26b, and miR-98) and found to be upregulated more than a 10-fold in active UC as compared to quiescent UC, CD, and controls. Two miRNAs, miR-125b-1* and let-7e*, were up-regulated more than 5-fold in quiescent UC compared to active UC, CD, and controls. Four of the seven miRNAs (miR-20b, miR-98, miR-125b-1*, and let-7e*) were validated by qPCR and found to be specifically upregulated in patients with UC. Using in silico analysis we found several predicted pro-inflammatory target genes involved in various pathways, such as mitogen-activated protein kinase and cytokine signaling, which are both key signaling pathways in UC.

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A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease

Cited by 511 publications

References 24 publications

Autophagy and human diseases

Autophagy and human diseases

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

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A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease

Cited by 511 publications

References 24 publications

Autophagy and human diseases

Autophagy and human diseases

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

Contact Info

Product

Resources

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miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis