Discovery of inflammatory bowel disease-associated miRNAs using a novel bipartite clustering approach

Altaf‐Ul‐Amin, Md.; Karim, Mohammad Bozlul; Hu, Pingzhao; Ono, Naoaki; Kanaya, Shigehiko

doi:10.1186/s12920-020-0660-y

Cited by 15 publications

(16 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, they found that let-7c may be highly related to IBD due to number of relevant miRNA-target interactions. 30 The miRNA let-7c also promotes M2 macrophage polarization (anti-inflammatory) and suppresses M1 (pro-inflammatory) polarization. 31 …”

Section: Discussionmentioning

confidence: 99%

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

Batra

Heier

Diaz-Calderon

et al. 2020

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Batra

Heier

Diaz-Calderon

et al. 2020

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

show abstract

“…As previously mentioned, the research field of miRNAs in IBD has grown rapidly after their discovery. Several studies have found significantly different profiles of hundreds of miRNAs 20 , 38 between IBD and healthy individuals, 39 paediatric and adult patients, 40 inflamed and non-inflamed mucosa, and in relation to disease activity. 15 , 35 , 37 , 40 To date, there are enough collected data to say that miRNAs are important regulatory factors that play a relevant role in the pathogenesis of IBD.…”

Section: The Relevance Of Mirna In Ibd Pathogenesismentioning

confidence: 99%

“…Additionally, a recent meta-analysis used a novel bipartite approach to find miRNA associated with IBD. 38 Among the most relevant was the Let-7 family. This is a multifaceted family of miRNA highly conserved across diverse animal species and related with cell proliferation, cell cycle, metabolism, and cell migration.…”

Section: The Relevance Of Mirna In Ibd Pathogenesismentioning

confidence: 99%

“…This is a multifaceted family of miRNA highly conserved across diverse animal species and related with cell proliferation, cell cycle, metabolism, and cell migration. 38 In more detail, the expression of multiple members of this family appears to be altered during inflammation. Regulated by NF-kB 46 and in direct relation with IL-6 expression, the Let-7 family is part of positive feedback loops that induce enhanced inflammatory responses and cell transformation.…”

Section: The Relevance Of Mirna In Ibd Pathogenesismentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA and Gut Microbiota: Tiny but Mighty—Novel Insights into Their Cross-talk in Inflammatory Bowel Disease Pathogenesis and Therapeutics

Casado‐Bedmar

Viennois

2021

Journal of Crohn's and Colitis

View full text Add to dashboard Cite

MicroRNAs (miRNAs), small non-coding RNAs, have recently been described as crucial contributors to intestinal homeostasis. They can interact with the gut microbiota in a reciprocal manner and deeply impact the host health status, leading to several disorders when unbalanced. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract that co-occurs with alterations of the gut microbiota, and whose aetiology remains largely unclear. On one hand, host miRNA could be playing a relevant role in IBD pathophysiology by shaping the gut microbiota. The gut microbiome, on the other hand, may regulate the expression of host miRNAs resulting in intestinal epithelial dysfunction, altered autophagy, and immune hyperactivation. Interestingly, it has been hypothesized that their reciprocal impact may be used for therapeutic goals. This review describes the latest research and suggests mechanisms through which miRNA and intestinal microbiota, as joint actors, may participate specifically in IBD pathophysiology. Furthermore, we discuss the diagnostic power and therapeutic potential resulting from their bidirectional communication after faecal transplantation, probiotics intake, anti-miRNAs or miRNA mimics administration. The current literature is summarized in the present work in a comprehensive manner hoping to provide a better understanding of the miRNA-microbiota crosstalk and to facilitate their application in IBD.

show abstract

“…Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a frequent gastrointestinal disease worldwide, which can affect any part of the digestive tract [ 1 ]. Epidemiological evidence indicates that the rate of IBD is increased every year, and there is currently no specific treatment for this disease [ 2 ]. IBD pathogenesis is a result of the interplay between environmental, genetic and immune response factors.…”

Section: Introductionmentioning

confidence: 99%

MiRNA-374b-5p and miRNA-106a-5p are related to inflammatory bowel disease via regulating IL-10 and STAT3 signaling pathways

Liu

et al. 2022

BMC Gastroenterol

View full text Add to dashboard Cite

Background Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is one of the most frequent gastrointestinal disorders worldwide. Although the actual etiology of IBD remains unclear, growing evidence suggests that CD4+ T cells-associated cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, are crucial for the occurrence of IBD. It has been reported that there is a positive association between miRNAs and IBD development. In this study, we investigated the roles of hsa-miRNA-374b-5p(miRNA-374b-5p) and hsa-miRNA-106a-5p(miRNA-106a-5p) in regulating IBD development. Methods Serum was obtained from vein blood of IBD patients and healthy controls, qRT-PCR was performed to study the expression of miRNA-374b-5p and miRNA-106a-5p. Furthermore, we investigate the effects of overexpression or inhibition of miRNA-374b-5p on naïve CD4 + T cell subsets differentiation from vein blood of healthy controls by RT-qPCR, flow cytometry and western blot. And more the prediction and confirmation of the targeting genes of miRNA-374b-5p and miRNA-106a-5p were performed by bioinformatics softwares and dual-luciferase reporter assay. Results The results showed that miRNA-106a-5p and miRNA-374b-5p were significantly overexpressed in IBD patients. MiRNA-374b-5p could enhance Th1/Th17 cell differentiation and was related to IBD pathogenesis. MiRNA-374b-5p overexpression induced the mRNA expression of IL-17A and IFN-γ, and suppressed that of IL-10 in T cells. MiRNA-374b-5p inhibition decreased the mRNA expression of IL-17A and IFN-γ, while upregulated that of IL-10 in T cells. These qPCR data were further verified at protein level by western blotting and flow cytometry. In addition, dual-luciferase reporter (DLR) assay indicated that miRNA-374b-5p was directly targeted by IL-10, a key anti-inflammatory cytokine for preventing the occurrence of IBD. Meanwhile, STAT3 was identified as a target gene of miRNA-106a-5p by DLR assays. Further analysis revealed that miRNA-374b-5p regulated JAK1 and STAT3 pathways in CD4+ T cells via IL-10/STAT3 axis. MiRNA-374b-5p overexpression remarkably decreased the mRNA expression and phosphorylated (ser-727) protein levels of STAT3, while miRNA-374b-5p inhibition had the opposite effects. Conclusion MiRNA-374b-5p and miRNA-106a-5p may contribute to IBD development by regulating IL-10/STAT3 signal transduction.

show abstract

Discovery of inflammatory bowel disease-associated miRNAs using a novel bipartite clustering approach

Cited by 15 publications

References 55 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

MicroRNA and Gut Microbiota: Tiny but Mighty—Novel Insights into Their Cross-talk in Inflammatory Bowel Disease Pathogenesis and Therapeutics

MiRNA-374b-5p and miRNA-106a-5p are related to inflammatory bowel disease via regulating IL-10 and STAT3 signaling pathways

Contact Info

Product

Resources

About