Similar Datasets
Project description:Hsa_circ_0001021 regulates intestinal epithelial barrier function via sponging miR-224-5p in ulcerative colitis
| PRJNA740289 | ENA
Project description:This project used glycomics approach to study the N-glycan present at the intestinal mucosal-luminal interface of pediatric UC patients.
2022-03-01 | PXD026327 | Pride
Project description:Inflammatory bowel disease is characterized by high levels of inflammation and loss of barrier integrity in the colon. The intestinal barrier is a dynamic network of proteins that encircle intestinal epithelial cells. miRNAs regulate protein-coding genes. In this study, miR-24 was found to be elevated in colonic biopsies and blood samples from ulcerative colitis (UC) patients compared with healthy controls. In the colon of UC patients, miR-24 is localized to intestinal epithelial cells, which prompted an investigation of intestinal epithelial barrier function. Two intestinal epithelial cell lines were used to study the effect of miR-24 overexpression on barrier integrity. Overexpression of miR-24 in both cell lines led to diminished transepithelial electrical resistance and increased dextran flux, suggesting an effect on barrier integrity. Overexpression of miR-24 did not induce apoptosis or affect cell proliferation, suggesting that the effect of miR-24 on barrier function was due to an effect on cell-cell junctions. Although the tight junctions in cells overexpressing miR-24 appeared normal, miR-24 overexpression led to a decrease in the tight junction-associated protein cingulin. Loss of cingulin compromised barrier formation; cingulin levels negatively correlated with disease severity in UC patients. Together, these data suggest that miR-24 is a significant regulator of intestinal barrier that may be important in the pathogenesis of UC.
| S-EPMC6723227 | biostudies-literature
Project description:The colonic inner mucus layer protects us from pathogen invasion and commensal-induced inflammation. Mucus abnormalities are common in ulcerative colitis (UC), but their cause and importance are unknown. The aim of this study was to determine the role of compositional mucus barrier alterations in UC. In this single-center case-control study, sigmoid colon biopsies were obtained from UC patients with ongoing inflammation (n=36) and in remission (n=28), and from 47 patients without inflammatory bowel disease. Mucus samples were collected from biopsies ex vivo, and their protein composition analyzed by mass spectrometry. Mucus barrier integrity and goblet cell response to microbial challenge were also assessed for a subset of patients. The core colonic mucus proteome was shown to consist of a small set of 29 secreted proteins. Patients with active UC had reduced levels of major structural components, including the mucin MUC2 (p<0.0001), also in mucus from non-inflamed segments, and their goblet cell secretory response to microbial stimulus was abrogated. Functional mucus barrier failure was observed in a subset of UC patients with and without active inflammation, and accompanied by alterations in proteins associated with mucus secretion and luminal organization. This study represents the first characterization and comparison of the mucus proteomes of the inflamed and non-inflamed colon. Core mucus structural components were reduced in active UC, also in mucus from non-inflamed segments. Thus, weakening of the mucus barrier is likely to occur early in UC pathogenesis, and represents a novel target for intervention.
2021-03-26 | PXD012632 | Pride
Project description:Background. Recent studies demonstrated that Aquamin®, a calcium-, magnesium-, and multiple trace element-rich natural product, improves barrier structure and function in colonoids obtained from the tissue of healthy subjects. The goal of the present study was to determine if the colonic barrier could be improved in tissue from subjects with ulcerative colitis (UC). Methods. Colonoid cultures were established with colon biopsies from 9 individuals with UC. The colonoids were then incubated for a 2-week period under control conditions (i.e., in culture medium with a final calcium concentration of 0.25 mM) or in the same medium supplemented with Aquamin® to provide 1.5 – 4.5 mM calcium. Effects on differentiation and barrier improvement were determined using several approaches: phase-contrast & scanning electron microscopy, quantitative histology & immunohistology, mass spectrometry-based proteome assessment and transmission electron microscopy. Results. While there were no gross changes in colonoid appearance, there was evidence of increased differentiation (larger lumen diameter and wall thickness) and greater expression of cytokeratin 20 (CK20) and lesser expression of Ki67 with the intervention. Aquamin®-treated colonoids demonstrated a modest up-regulation of tight junctional proteins but stronger induction of adherens junction proteins and desmosomal proteins. Increased desmosomes were seen at the ultrastructural level. Proteomic analysis also demonstrated increased expression of basement membrane proteins and hemidesmosomal components. Proteins expressed at the apical surface (mucins and trefoils) were also increased as were several additional proteins with anti-microbial activity or that modulate inflammation. Similarly, growth and cell cycle regulatory proteins (e.g., Ki67, nucleophosmin, and stathmin) were significantly down-regulated. Laminin interactions, fibronectin matrix formation and extracellular matrix organization were the top three up-regulated pathways with the intervention. Conclusion. A majority of individuals including patients with UC do not reach the recommended daily intake for calcium and other minerals. To the extent that such deficiencies might contribute to the weakening of the colonic barrier, the findings employing UC tissue-derived colonoids here suggest that adequate mineral intake might improve the colonic barrier
2020-12-17 | PXD020244 | Pride
Project description:The samples are a part of a study aiming at diagnosing ulcerative colitis from genome-wide gene expression analysis of the colonic mucosa. Colonic mucosal samples were collected as endoscopic pinch biopsies from ulcerative colitis patients and from control subjects. Samples with and without macroscopic signs of inflammation were collected from the patients. Experiment Overall Design: The series contain eight UC samples with macroscopic signs of inflammation, 13 UC smaples without macroscopic signs of inflammation, five control subjects.
2008-06-20 | E-GEOD-9452 | biostudies-arrayexpress
Project description:Recently, increased studies have shown the important regulatory role of circular RNA (circRNA) in cancer progression and development, including glioblastoma (GBM). However, the function of circRNAs in glioblastoma is still largely unclear. Here, we state that circFGFR1 is elevated in glioma cells, resulting in aggravated glioma aggravated malignancy. The upregulation of circFGFR1 also promotes glioma growth in mouse xenograft models. Furthermore, CXCR4 level in glioma cells is positively correlated with circFGFR1 level, and higher CXCR4 expression is found in circFGFR1 overexpression groups. The effect of circFGFR1 on glioma malignancy is abolished in CXCR4 knockout cells. Then, RIP, RNA pull-down, and luciferase reporter assay results showed that hsa-miR-224-5p directly binds to circFGFR1 and CXCR4 mRNA. The CXCR4 3'-untranslated region (UTR) activated luciferase activity was reduced with hsa-miR-224-5p transfection, while it is reversed when cotransfected with circFGFR1, indicating that circFGFR1 acts as a hsa-miR-244-5p sponge to increase CXCR4 expression. The hsa-miR-224-5p expression is negatively corrected with the glioma malignancy through inhibiting CXCR4 level. Besides, the circFGFR1-induced regulation in glioma malignancy is also abrogated in hsa-miR-224-5p knockout cells. Taken together, our findings suggest that circFGFR1 plays a critical role in the tumorigenic behaviors in glioma cells by upregulating CXCR4 expression via sponging to hsa-miR-224-5p. These findings provide a new perspective on circRNAs during GBM development.
| S-EPMC8764274 | biostudies-literature
Project description:MicroRNAs have been associated with the pathogenesis of intestinal diseases such as colon cancer and are deregulated in the inflammatory environment of intestinal mucosa in UC patients. The effects of microRNAs on immunological factors have been described before, however, there is no evidence that they have an effect on alarmins that impact on the pathophysiology of UC. Our goal is to identify deregulated miRNAs to be paired with potential target mRNAs. We used microarrays to compare inflamed and non inflamed mucosa from chilean ulcerative colitis patients
2019-10-07 | GSE133059 | GEO
Project description:Our group used rectal biopsies from patients with active ulcerative colitis (UC) and differential response to glucocorticoid treatment, to generate a predictive computational strategy based on systems biology. Contrasting mRNA and miRNAs intestinal expression profiles with updated molecular information related to UC and glucocorticoids, we were able to identify a mechanism of action (MoA) associated with corticosteroid failure in UC. ith the aim of transferring these results to clinical practice, the MoA-models created previously were implemented with plasmatic miRNAs profiles, to describe in silico non-invasive potential biomarkers of glucocorticoid refractoriness. Small RNA-seq analysis was perfomed using Illumina next generation sequencing and standard statistical criteria were applied to compare the miRNA profiles, incluidng paired samples before clucocorticoid treatment to the third day of the steroidal treatment. The selection these miRNA with predictive capacity was done using two complementary strategies: the first one using all the obtained miRNAs, and the second taking into account those miRNAs that are directly related to MoA, through various statistical restrictions (RELIEF, ENTROPY + CORRELATION, WILCOXON, ROC, and simple REGRESSION). These computational approaches from all miRNAs identified hsa-miR218-5p as the best to classify patients according their respond at basal time (Accuracy = 84.21%, Generalization Capability = 84.21%, Sensitivity = 100% and Specificity = 66.67%). In addition, the combination of this miRNA with hsa-miR6754-5p and hsa-miR4767, increases the diagnosis accuracy of the disease (Accuracy = 94.74%, Generalization Capability = 75.44%, Sensitivity = 70% and specificity = 81.48%). On the other hand, the combination of hsa-miR218-5p and the plasma levels of the Protein C Reactive increases the ability to classify patients towards their response to glucocorticoids up to 89%. Taking in account all this data, we can conclude that by means of a computer strategy based on Biology of Systems we have identified the plasmatic miR-218-5p as a potential biomarker to glucocorticoid response in UC before start the treatment.
2022-03-30 | GSE122618 | GEO
Project description:Background: This study addresses whether existing specific transcriptional profiles can improve and support the current status of the definition of ulcerative colitis (UC) remission apart from the existing endoscopic, histologic, and laboratory scoring systems. For that purpose, a well-stratified UC patient population in remission was compared to active UC and control patients and was investigated by applying the next-generation technology RNA-Seq. Methods: Mucosal biopsies from patients in remission (n = 14), patients with active UC (n = 14), and healthy control patients (n = 16) underwent whole-transcriptome RNA-Seq. Principal component analysis, cell deconvolution methods, gene profile enrichment, and pathway enrichment methods were applied to define a specific transcriptional signature of UC in remission. Results: Analyses revealed specific transcriptional signatures for UC in remission with increased expression of genes involved in O-glycosylation (MUC17, MUC3A, MUC5AC, MUC12, SPON1, B3GNT3), ephrin-mediated repulsion of cells (EFNB2E, EFNA3, EPHA10, EPHA1), GAP junction trafficking (TUBA1C, TUBA4A, TUBB4B, GJB3, CLTB), and decreased expression of several toll-like receptors (TLR1, TLR3, TLR5, TLR6). Conclusions: This study reveals specific transcriptional signatures for remission. Partial restoration and improvement of homeostasis in the epithelial mucus layer and revival of immunological functions were observed. A clear role for bacterial gut flora composition can be implied. The results can be useful for the development of treatment strategies for UC in remission and may be useful targets for further investigations aiming to predict the outcome of UC in the future.
2020-01-18 | GSE128682 | GEO