Increased expression of microRNA in the inflamed colonic mucosa of patients with active ulcerative colitis

Takagi, Tomohisa; Naito, Yuji; Mizushima, Katsura; Hirata, Ikuhiro; Yagi, Nobuaki; Tomatsuri, Naoya; Ando, Takashi; Oyamada, Yuichi; Isozaki, Yutaka; Hongo, Hitomi; Uchiyama, Kazuhiko; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Yoshikawa, Toshikazu

doi:10.1111/j.1440-1746.2009.06216.x

Cited by 164 publications

(122 citation statements)

References 20 publications

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“…When comparing the lists, no miRNA duplicates were found. Several of the differentially expressed miRNAs (such as miR23a, miR-155, miR-16, miR-150, miR-346, and miR-126) reported to be associated with UC in previous studies [36][37][38] were also identified within our analyses (Tables 2 and 3). However, in addition to these previously reported miRNAs, we additionally identified five potential miRNAs, miR-20b, miR-99a, miR-203, miR-26b, and miR-98 to be differentially up-regulated more than a 10-fold in active UC compared to inactive UC, active CD, inactive CD, and controls (Table 2).…”

Section: Statistical Analysis Mirna Data Analysissupporting

confidence: 54%

“…Among the miRNAs with the strongest differential power from the microarray expression data we identified several differentially expressed miRNAs (such as miR23a, miR-155, miR-16, miR-150, miR-346, and miR-126) previously reported to be associated with UC [36][37][38] . However, we also identified seven miRNAs (miR-20b, miR99a, miR-203, miR-26b, miR-98, miR-125b-1*, and let7e*) that were not previously reported to be involved in IBD [27] .…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Statistical Analysis Mirna Data Analysissupporting

confidence: 54%

Section: Discussionmentioning

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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“…Furthermore, they found that miR192 participated in the regulation of chemokine production in colonic epithelial cells. Since 2008, some new research in active UC and healthy controls has confirmed the upregulation of miR-21 [25,118] , miR 29a [119] , and miR126 [120] , and identified additional upregulated miRNAs, including miR7, miR29b, miR126*, miR1273p, miR135b, miR223 and miR 3243p [119] , miR31 [119,121] , miR150 [26] , miR155 [118] , miR146a, miR206, and miR424 [121] , and miR 20b and miR125b1* [122] . In contrast, miR1885p, miR215, miR320a, miR346 [119] , and miR200b [123] were downregulated in colon tissues from active UC patients compared with healthy controls.…”

Section: Mirnas In Ucmentioning

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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“…При активном ЯК изменялась экспрессия 11 микроРНК (miR-16, miR-21, miR-23a, miR-24, miR-29a, miR-126, miR-195, miR-let-7f, miR-192, miR-375, and miR-422b), осо-бое внимание обращено на изменение экспрессии miR-192. После публикации этого исследования, по-явились другие работы, целью которых была иденти-фикация микроРНК, определение патогенетической роли микроРНК и выяснение закономерностей экс-прессии микроРНК в генезе ЯК и БК [52].…”

Section: лабораторные биомаркеры язвенного колитаunclassified

“…Экспрессия miR-155 повышается при ЯК [52], сле-дом увеличивается и синтез ФНО-α. В перспективе ученые планируют использовать этот факт в созда-нии иммуноподавляющей мишени терапии.…”

Section: лабораторные биомаркеры язвенного колитаunclassified

The Modern View of the Pathogenesis and Laboratory Diagnostics of Ulcerative Colitis (Literature Review)

2017

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РезюмеОсновной теорией патогенеза воспалительных заболеваний кишечника в настоящее время считается активация иммунного ответа к анти-генам собственной кишечной микрофлоры у генетически предрасположенных лиц. «Золотым стандартом» диагностики язвенного колита является колоноскопия с морфологическим исследованием биоптата. В связи с инвазивностью, сложностью в подготовке и проведении, высокой стоимостью эндоскопического исследования, существует потребность в применении лабораторных биомаркеров язвенного коли-та, с помощью которых можно выделить группу лиц, подлежащих углубленному инструментальному обследованию. В обзоре освещается современный взгляд на патогенез заболевания, специфические лабораторные биомаркеры в диагностике язвенного колита, для мониторин-га эффективности проводимой терапии, в качестве предикторов тяжелого течения язвенного колита, прогнозирования терапевтического ответа и раннего выявления рецидива. AbstractThe basic theory of the pathogenesis of inflammatory bowel disease (IBD) is currently considered a violation of immune activation and immune response against its own antigens to the intestinal flora in genetically predisposed individuals. "The gold standard" diagnosis of UC is colonoscopy with biopsy morphological study. Due to the invasiveness, complexity in the preparing and conducting, the high cost of endoscopy there is a need in the application of laboratory biomarkers UC, with which you can select a group of persons subject to an in-depth examination of the instrumental. The review highlights the modern view of the pathogenesis of the disease, the ability to use a variety of laboratory biomarkers in the diagnosis of UC, for monitoring the effectiveness of the therapy, as predictors of severe course of UC, therapeutic response prediction and early detection of recurrence.

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Increased expression of microRNA in the inflamed colonic mucosa of patients with active ulcerative colitis

Abstract: Upregulated miRNA may be responsible for the development of intestinal inflammation in UC.

Cited by 164 publications

References 20 publications

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

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

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

The Modern View of the Pathogenesis and Laboratory Diagnostics of Ulcerative Colitis (Literature Review)

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Increased expression of microRNA in the inflamed colonic mucosa of patients with active ulcerative colitis

Abstract: Upregulated miRNA may be responsible for the development of intestinal inflammation in UC.

Cited by 164 publications

References 20 publications

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

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

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

The Modern View of the Pathogenesis and Laboratory Diagnostics of Ulcerative Colitis (Literature Review)

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Product

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

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