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Circulating microRNAs Suggest Networks Associated with Biological Functions in Aggressive Refractory Type 2 Celiac Disease.

ABSTRACT: Despite following a gluten-free diet, which is currently the only effective therapy for celiac disease, about 5% of patients can develop serious complications, which in the case of refractory type 2 could evolve towards intestinal lymphoma. In this study, we have identified a set of 15 microRNAs in serum discriminating between the two types of refractory disease. Upregulated miR-770-5p, miR-181b-2-3p, miR-1193, and miR-1226-3p could be useful for the better stratification of patients and the monitoring of disease development, while miR-490-3p was found to be dysregulated in patients with refractory type 1. Finally, by using bioinformatic tools applied to the analysis of the targets of dysregulated microRNAs, we have completed a more precise assessment of their functions. These mainly include the pathway of response to Transforming Growth Factor β cell-cell signaling by Wnt; epigenetic regulation, especially novel networks associated with transcriptional and post-transcriptional alterations; and the well-known inflammatory profiles.

SUBMITTER: Bianchi N

PROVIDER: S-EPMC9219665 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Circulating microRNAs Suggest Networks Associated with Biological Functions in Aggressive Refractory Type 2 Celiac Disease.

Bianchi Nicoletta N Doneda Luisa L Elli Luca L Taccioli Cristian C Vaira Valentina V Scricciolo Alice A Lombardo Vincenza V Terrazzan Anna A Colapietro Patrizia P Terranova Leonardo L Bergamini Carlo C Vecchi Maurizio M Scaramella Lucia L Nandi Nicoletta N Roncoroni Leda L

Biomedicines 20220614 6

Despite following a gluten-free diet, which is currently the only effective therapy for celiac disease, about 5% of patients can develop serious complications, which in the case of refractory type 2 could evolve towards intestinal lymphoma. In this study, we have identified a set of 15 microRNAs in serum discriminating between the two types of refractory disease. Upregulated miR-770-5p, miR-181b-2-3p, miR-1193, and miR-1226-3p could be useful for the better stratification of patients and the mon ...[more]

PMID: 35740429

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Project description:BackgroundCeliac Disease (CD) is a multifactorial autoimmune enteropathy (with a prevalence of approximately 1% worldwide) that exhibits a wide spectrum of clinical, serological and histological manifestations. For the diagnosis of paediatric CD, the gold standard is the combination of serological tests (with high TGA-IgA values greater than 10 times the upper limit of normal) and duodenal biopsy (with a positive TGA-IgA but low titer). Therefore, a diagnostic test that totally excludes an invasive approach has not been discovered so far and the discovery of novel biological markers would represent an undoubted advantage for the diagnosis of CD and prognostic evaluation. MicroRNAs (miRNAs), small non-coding RNAs (18-22 nucleotides) that regulate gene expression at post-transcriptional level and play important roles in many biological processes, represent a novel class of potential disease biomarkers. Their presence in biological fluids (i.e., serum, plasma, saliva, urine) provides the opportunity to employ circulating miRNAs as novel non-invasive biomarkers.MethodsIn our prospective observational study, we examined the expression of circulating miRNAs in a cohort of CD patients (both at diagnosis and on gluten-free diet, respectively referred as CD and GFD) compared to healthy controls. By small RNA-Seq we discovered a set of circulating miRNAs that were further validated by qPCR with specific assays.FindingsWe found that out of the 13 miRNAs able to discriminate the three groups (i.e., CD, GFD and controls), three of them, namely miR-192-5p, miR-215-5p and miR-125b-5p (alone or in combination), were able to discriminate these three groups with high accuracy and specificity.InterpretationOur conclusions emphasize that these circulating miRNAs can be employed not only for the diagnosis of CD patients with a low TGA-IgA titer but also to monitor the adherence to a gluten-free diet by CD patients. In conclusion, we suggest the use of the circulating miRNAs identified in this work as a novel diagnostic and follow-up tool for paediatric CD.FundingThis work was supported by Fondazione Celiachia Onlus (FC) Grant n° 018/FC/2013 and by Italian Ministry of Health (Ricerca Corrente).

Dataset Information

Circulating microRNAs Suggest Networks Associated with Biological Functions in Aggressive Refractory Type 2 Celiac Disease.

Publications

Circulating microRNAs Suggest Networks Associated with Biological Functions in Aggressive Refractory Type 2 Celiac Disease.

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