Functional role and therapeutic targeting of microRNAs in inflammatory bowel disease

Soroosh, Artin; Κουτσιούμπα, Μαρίνα; Pothoulakis, Charalabos; Iliopoulos, Dimitrios

doi:10.1152/ajpgi.00268.2017

Cited by 55 publications

(34 citation statements)

References 69 publications

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“…We and others have previously described the utility of miRNAs as biomarkers in IBD. 14 , 16–18 Adding to our previous miRNA studies in pediatric IBD, here we have now identified 8 serum miRNA biomarkers that are associated with clinical response to anti-TNF-α therapy (after weeks) and GC treatment (after weeks) 14 but (with the exception of miR-26b) not with shorter courses of GCs (after days). These are miR-126, miR-146a, miR-146b, miR-26a, miR-26b, miR-320a, miR-454, and let-7c.…”

Section: Discussionmentioning

confidence: 85%

Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease

Batra

Heier

Diaz-Calderon

et al. 2020

Inflammatory Bowel Diseases

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Background We sought to identify microRNAs (miRNAs) associated with response to anti-TNF-α or glucocorticoids in children with inflammatory bowel disease (IBD) to generate candidate pharmacodynamic and monitoring biomarkers. Methods Clinical response was assessed by Pediatric Crohn’s Disease Activity Index and Pediatric Ulcerative Colitis Activity Index. Quantitative real-time polymerase chain reaction via Taqman Low-Density Array cards were used to identify miRNAs in a discovery cohort of responders (n = 11) and nonresponders (n = 8). Seven serum miRNAs associated with clinical response to treatment, along with 4 previously identified (miR-146a, miR-146b, miR-320a, miR-486), were selected for further study. Candidates were assessed in a validation cohort of serum samples from IBD patients pre- and post-treatment and from healthy controls. Expression of miRNA was also analyzed in inflamed mucosal biopsies from IBD patients and non-IBD controls. Results Discovery cohort analysis identified 7 miRNAs associated with therapeutic response: 5 that decreased (miR-126, miR-454, miR-26b, miR-26a, let-7c) and 2 that increased (miR-636, miR-193b). In the validation cohort, 7 of 11 candidate miRNAs changed in the same direction with response to anti-TNF-α therapies, glucocorticoids, or both. In mucosal biopsies, 7 out of 11 miRNAs were significantly increased in IBD vs healthy controls. Conclusions Five candidate miRNAs associated with clinical response and mucosal inflammation in pediatric IBD patients were identified (miR-126, let-7c, miR-146a, miR-146b, and miR-320a). These miRNAs may be further developed as pharmacodynamic and response monitoring biomarkers for use in clinical care and trials.

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Section: Discussionmentioning

confidence: 85%

Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease

Batra

Heier

Diaz-Calderon

et al. 2020

Inflammatory Bowel Diseases

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“…Therefore, identification of IBD-associated miRNA autophagic networks and exploration of specific miRNAs as targets for the treatment of IBD is very important. There are two completed phase I trials (NCT00688012 for a single ascending dose and NCT00979927 for multiple ascending doses; drug: SPC3649) funded by Santaris Pharma related to a locked nucleic acid- (LNA-) modified oligonucleotide that specifically inhibits endogenous miR-122, resulting in prolonged dose-dependent reductions in hepatitis C virus (HCV) RNA levels without evidence of viral resistance [ 25 , 100 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several review articles to date have discussed the role of miRNAs in IBD [ 8 , 16 , 18 , 19 , 21 – 25 ], However, there are no reviews that focus on the IBD field and on miRNAs that regulate autophagy and associated pathways. Elucidation of the interaction between miRNAs and autophagy in IBD-specific mechanisms will help to explain the occurrence, development, and future molecular targets of IBD therapy.…”

Section: Introductionmentioning

confidence: 99%

The Role of Autophagy and Related MicroRNAs in Inflammatory Bowel Disease

Wang

Huang

Zhou

et al. 2018

Gastroenterology Research and Practice

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Accumulating evidence demonstrates that microRNA- (miR-) mediated posttranscriptional regulation plays an important role in autophagy in inflammatory bowel disease (IBD), a disease that is difficult to manage clinically because of the associated chronic recurrent nonspecific inflammation. Research indicates that microRNAs regulate autophagy via different pathways, playing an important role in the IBD process and providing a new perspective for IBD research. Related studies have shown that miR-142-3p, miR-320, miR-192, and miR-122 target NOD2, an IBD-relevant autophagy gene, to modulate autophagy in IBD. miR-142-3p, miR-93, miR-106B, miR-30C, miR-130a, miR-346, and miR-20a regulate autophagy by targeting ATG16L1 through several different pathways. miR-196 can downregulate IRGM and suppress autophagy by inhibiting the accumulation of LC3II. During the endoplasmic reticulum stress response, miR-665, miR-375, and miR-150 modulate autophagy by regulating the unfolded protein response, which may play an important role in IBD intestinal fibrosis. Regarding autophagy-related pathways, miR-146b, miR-221-5p, miR-132, miR-223, miR-155, and miR-21 regulate NF-κB or mTOR signaling to induce or inhibit autophagy in intestinal cells by releasing anti- or proinflammatory factors, respectively.

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“…Hong et al [109], via RNA-seq, pinpointed differences between the inflamed and non-inflamed intestinal mucosa of CD patients and healthy controls. Of high interest in recent years is the study of noncoding RNAs and their role, as depicted in reviews and original articles [110][111][112][113][114][115][116].…”

Section: Transcriptomics In Ibdmentioning

confidence: 99%

Systems biology in inflammatory bowel diseases: on the way to precision medicine

Dovrolis

Filidou

Kolios

2019

aog

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Inflammatory bowel diseases (IBD) are chronic and recurrent inflammatory disorders of the gastrointestinal tract. The elucidation of their etiopathology requires complex and multiple approaches. Systems biology has come to fulfill this need in approaching the pathogenetic mechanisms of IBD and its etiopathology, in a comprehensive way, by combining data from different scientific sources. In combination with bioinformatics and network medicine, it uses principles from computer science, mathematics, physics, chemistry, biology, medicine and computational tools to achieve its purposes. Systems biology utilizes scientific sources that provide data from omics studies (e.g., genomics, transcriptomics, etc.) and clinical observations, whose combined analysis leads to network formation and ultimately to a more integrative image of disease etiopathogenesis. In this review, we analyze the current literature on the methods and the tools utilized by systems biology in order to cover an innovative and exciting field: IBD-omics.

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Functional role and therapeutic targeting of microRNAs in inflammatory bowel disease

Cited by 55 publications

References 69 publications

Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease

Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease

The Role of Autophagy and Related MicroRNAs in Inflammatory Bowel Disease

Systems biology in inflammatory bowel diseases: on the way to precision medicine

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