Author: Poorani Sivaraman
Publisher:
ISBN:
Category :
Languages : en
Pages : 372
Get Book Here
Book Description
MicroRNAs (miRNAs) are short non-coding RNAs of 19-22 nucleotides that regulate gene expression. They target the 3'-untranslated region (UTR), and sometimes the 5'-UTR, of messenger RNAs (mRNAs), and suppress protein translation and/or trigger mRNA degradation. Since their discovery, miRNAs have been implicated in various regulatory pathways and diseases. New miRNAs are constantly being discovered that are yet to be fully characterised or validated. Few miRNAs and their genes have been well studied and characterised. Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, whose etiology appears to involve genetic, environmental, and immunological factors. The Krissansen laboratory recently obtained evidence for the overexpression of hsa-miR-595 and hsa-miR- 1246 in the sera of patients suffering from severe forms of IBD. It was hypothesized that both miRNAs might be involved in the maintenance of the epithelial barrier function of the intestine, and/or in immune regulation. There is a lack of information in the published literature regarding these miRNAs, their gene features, and their target mRNAs. Research was carried out to study the characteristics of the genes that encode hsa-miR-595 and hsa-miR-1246, to identify potential mRNA targets of these miRNAs, and determine whether the miRNAs are involved in disrupting the tight junctions formed by intestinal epithelial cells. Bioinformatics analyses were carried out to identify features of the genes encoding miR-595 and miR-1246 to provide evidence of the authenticity of these miRNAs. The NCBI GenBank database was searched for expressed sequence tags (ESTs) encoding the 5'- and 3'-flanking regions of the genes to provide evidence that the genes are transcribed. In silico screening of various miRNA target databases for mRNA targets of these miRNAs was carried out. 3'-UTR luciferase reporter assays were developed to determine whether selected targets were authentic. The ability of miR-595 and miR-1246 to inhibit the expression of selected mRNA targets expressed by the human epithelial colorectal adenocarcinoma (Caco- 2) cell line was examined. An attempt was made to get Caco-2 cells to form spheroids during 3D cell culture, in order to subsequently use the spheroids to demonstrate disruption of tight junctions by miR-595 and miR-1246. Bioinformatics analyses indicated that both hsa-miR-595 located at chromosome 7q36.3 and hsa-miR-1246 located at chromosome 2q31.1 potentially contain common gene features such as putative promoters, transcription start sites, CpG islands, and polyadenylation signal sites. The hsa-miR-595 gene is intragenic, being located within intron 1 of the protein tyrosine phosphate receptor type 2, N polypeptide (PTPRN2) gene. In contrast, hsa-miR-1246 is intergenic, being located between the metaxin 2 (MTX-2) and nuclear factor, erythroid 2-like 2 (NFE2L2) genes. Experimental work needs to be carried out to prove whether the predicted gene features identified are involved in the transcription and regulation of these miRNA genes. ESTs encoding each gene were identified in cDNA libraries prepared from a variety of different tissues, indicating that the miR-595 and miR-1246 genes are actively transcribed in different tissues. A literature search revealed that hsa-miR-1246 had been cross-mapped to chromosome 17, being located within the gene encoding the small nuclear RNA RNU2-1. The U2 locus consists of 6 to more than 30 tandem repeats indicating that this locus gives rise to multiple copies of hsa-miR-1246. It is not known whether the elevated levels of hsa-miR- 1246 in the sera of IBD patients arise from overexpression of hsa-miR-1246 on chromosome 2 or chromosome 17, or both. A search of various miRNA target databases indicated that either miR-595 or miR-1246, or both, targeted CDH2, PARD6A, NCAM1, FGFR2, AJAP1, and DYRK1A. MiR-595 had previously been reported to target the tight junction protein PARD6A, causing disruption of the permeability of epithelia, which might be expected to have important implications for IBD. MiR-1246 had previously been reported to target DYRK1A, causing increased expression of the transcription factor NFAT1c that induces the expression of inflammatory cytokines, and which might be expected to have important implications for IBD. An attempt was made to experimentally validate the above mRNA targets using a 3'-UTR luciferase reporter assay, but the assay was not successful due to technical issues and time constraints. Several attempts were made to form hollow spheroids from Caco-2 cells to mimic the gut wall and lumen, but the spheroids produced were not correctly formed in that they appeared to be deflated. In summary, the experimental approaches tackled were not successful in providing conclusive evidence about the authenticity of the mRNA targets, but will be useful for future validation. In conclusion, the results of the computational analyses and experimental approaches attempted provide a framework, and basis for future investigation of miR-595 and miR-1246, and their mRNA targets. In the future, these miRNAs could be investigated for their utility in diagnosing the severity of IBD. Inhibitors of the miRNAs could be investigated for their ability to prevent or attenuate disease symptoms.
Author: Kurt Fisher
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages :
Get Book Here
Book Description
Idiopathic inflammatory bowel disease (IBD) is a complex set of disorders that predominantly includes ulcerative colitis and Crohn's disease. The pathogenesis of IBD is multifactorial including genetic, infectious, and immunologic factors. MicroRNAs belong to a class of noncoding small RNAs that posttranscriptionally regulate gene expression, and they are an emerging class of genetic modifiers of IBD. Here, we focus on the use of unique microRNA expression patterns as biomarkers to classify and prognosticate disease severity in both mucosal tissue and serum from patients with either ulcerative colitis or Crohn's disease. Furthermore, we discuss specific microRNAs with respect to their roles in IBD pathogenesis and fibrosis. We also discuss the role of microRNAs in IBD-associated carcinogenesis, including their role as biomarkers, tumor suppressors, and oncogenes. Finally, we discuss the emerging therapeutic applications of microRNA manipulation to lessen the effect of IBD and its sequelae. Recent discoveries of the diverse roles of microRNAs in IBD pathogenesis have the potential to provide new targeted therapeutics for personalized medicine.
Author: Nik Sheng Ding
Publisher: Springer
ISBN: 3030114465
Category : Medical
Languages : en
Pages : 355
Get Book Here
Book Description
This book provides a comprehensive and complete overview of biomarkers in clinical practice for inflammatory bowel disease (IBD) bringing together the literature in a clear and concise manner. The book bridges the gap between growing knowledge at the bench and current and future applications of biomarkers in clinical practice. The central structure of the book focuses on prognostic and predictive biomarkers in IBD with an emphasis on the fields of research and scientific techniques (genomics, proteomics and metabonomics) that have led to biomarker discovery and places these biomarkers within a clinical context to help understand their utility in clinical practice. This book will be of use to clinicians who have an interest in using biomarkers in clinical practice as well as clinician researchers and scientists involved in the biomarker research pipeline. The author team comprises experts from around the world in order to bring together the literature in an effort to inform clinicians and researchers about the current state-of-the art in biomarker discovery. It is intended to assist future research efforts and indicate how biomarkers might be best applied to clinical practice both at present and in the future.
Author: Catherine M. Greene
Publisher: Springer
ISBN: 3319136895
Category : Medical
Languages : en
Pages : 242
Get Book Here
Book Description
The book serves as a comprehensive resource for scientists and clinicians studying the role of non-coding RNAs in inflammation (viral infections, wound inflammation), human inflammatory diseases (i.e. rheumatoid arthritis, Crohn’s disease, diabetes) and innate immunity. It provides a universal reference work comprising both basic and specialized information. Given that ncRNAs represent new therapeutic targets, this volume will also be of interest to industrial biomedical researchers and those involved in drug development.
Author: Mauro D'Amato
Publisher: Springer Science & Business Media
ISBN: 1461482569
Category : Medical
Languages : en
Pages : 344
Get Book Here
Book Description
Research in Crohn’s disease (CD) and ulcerative colitis (UC), together known as the inflammatory bowel diseases (IBD), has truly seen a revolution in the last 5-10 years. This book examines how these genetic discoveries have led to the identification of biological functions not previously associated with IBD pathophysiology (e.g. autophagy), how multiple genetic risk factors for IBD converge on given biological functions and that together the identified variants in these genes have predisposing and protective roles (e.g. the multiple variants in the receptor for the IL23 cytokine and its signaling cascade), and how having such a large number of known genetic risk factors has changed our understanding not only about the genetic and molecular overlap between CD and UC, but also between these diseases and other chronic inflammatory diseases (e.g. psoriasis, multiple sclerosis, type 1 diabetes and many others).
Author: Maleene Patel
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Author: Peter Igaz
Publisher: Springer
ISBN: 3034809557
Category : Medical
Languages : en
Pages : 292
Get Book Here
Book Description
MicroRNAs as the endogenous mediators of RNA interference have experienced an unprecedented career in recent years, highlighting their pathogenic, diagnostic and potential therapeutic relevance. Beside tissue microRNAs, they are also found in body fluids, most notably in blood. Significant differences of circulating microRNA levels have been found in various diseases, making them candidates for minimally invasive markers of disease, for example tumor malignancy. The book focuses on the potential diagnostic applicability of circulating microRNAs in various diseases and their potential biological significance.
Author: Charlotte Hedin
Publisher: Springer Nature
ISBN: 3030287033
Category : Medical
Languages : en
Pages : 399
Get Book Here
Book Description
This book reaches out to a wide variety of professionals in the biomedical field with an interest in inflammatory bowel disease (IBD). Enormous progress has been made in the last few years since the publication of the first edition in the study of complex diseases and IBD, with hundreds of genomic regions identified that are associated with increased risk. Authored by leading clinical and research scientists in the field, the book includes state-of-the art synopses of recent genetic findings, and their interpretation for current and future exploitation in translational approaches to personalized medicine in IBD. The book also covers risk prediction, improved diagnostic and therapeutic precision, dissection of disease phenotypes and subtypes, identification of biomarkers, and host gene-microbiota interactions of clinical relevance.
Author: Jaishree Paul
Publisher: CRC Press
ISBN: 1351679872
Category : Medical
Languages : en
Pages : 231
Get Book Here
Book Description
This book explores the role of miRNA as therapeutic agents, the progress made in this direction and the problems that need to be addressed for miRNA based therapies to become successful. It also discusses the basic biology of miRNA sythesis, regulation, and their role in disease biology.
Author: Sean Henry Manning
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract affecting over 3 million adults in the United States. Despite being widespread, reliable early diagnostic tests are not available. In order to remedy this, we evaluated exosomal small RNA (smRNA), specifically targeting microRNA (miRNA) and piRNA from the stool samples of IBD model mice as a potential diagnostic marker. Exosomes are a sub-type of extracellular nano-sized vesicles that mediate extracellular communication via transport of various biomolecules such as coding and non-coding RNAs (e.g., miRNA). The exosome communication process impacts several physiological and pathological pathways by modulating protein expression. Recently, investigation into the applicability of exosomal miRNA as diagnostic biomarkers has grown significantly. Here, we evaluated exosomal smRNA, specifically targeting miRNA, and piRNA from the stool samples of IBD model mice as potential markers of IBD. We used interleukin 10 knockout mice (IL-10KO), a validated model for IBD, and compared their fecal exosomal small RNA to that of wild type C57BL/6J (B6) mice. Stool samples were specifically chosen because they are readily available and collection is noninvasive. Feces were collected weekly for a total of 7 weeks from 28, conventionally housed, 4-week-old IL-10KO mice. Equal numbers of males (n=7), and females (n=7) were randomly assigned to each group. Additionally, a modified Crohn's disease activity index was used to score each mouse's clinical condition twice a week. At the end of the experimental period, the GI tract was collected, and disease severity scored. Histopathology showed a significant increase in inflammation and proliferation within the proximal and distal large intestines. In total, 12 smRNA's were found that are modulated during the development of IBD in our mouse model. Their unique expression patter may help differentiate IBD from related diseases and allow for earlier and less invasive diagnosis.
