MiR-4668 as a Novel Potential Biomarker for Eosinophilic Esophagitis

Abstract

Introduction Eosinophilic esophagitis (EoE) is a clinico-pathological diagnosis characterized by esophageal dysfunction and eosinophilic infiltration of the esophagus. Demonstration of esophageal eosinophilia (more than 15 eosinophils/hpf) in biopsy specimen obtained by esophagogastroduodenoscopy (EGD) continues to be the gold standard for diagnosis and monitoring of response to therapy. There is a growing necessity for non-invasive biomarkers that can accurately diagnose this condition and assess response to therapy. While microRNAs (miRNA) are being investigated in allergic diseases, including EoE, not many studies have explored the role of salivary miRNAs in EoE. MiR-4668-5p is a particularly interesting candidate, as it is predicted to regulate TGF-beta signaling and has not previously been identified as a target in any allergy disease. We sought to further investigate the role of miR-4668 as a biomarker to characterize and monitor response to treatment with swallowed topical glucocorticoids. Methods After IRB approval, twenty-two adult patients with EoE were randomly enrolled to provide a saliva sample before and after 2 months of swallowed fluticasone therapy. Differences of miRNA expression before and after treatment were analyzed by paired T-test. A significance cutoff of <0.05 was used for all analyses. Results Expression of miR-4668 was higher in EoE vs. non-EoE subjects. The level of miR-4668 decreased in all subjects except one, with a mean fold change 0.49 ± 0.25. There was an association between miRNA expression and number of positive aeroallergens. The miR-4668 high group had a higher number of positive aeroallergen tests, while the miR-4668 low group had a greater number of subjects with drug allergies. Conclusions In this study, we identified that salivary miRNAs may serve as biomarkers to characterize EoE and response to topical corticosteroids. We specifically identified miR-4668 as a novel potential biomarker, which was not previously discovered as a target in EoE or any other allergic disease.

Expression and Secretion of Circular RNAs in the Parasitic Nematode, Ascaris suum

“…Human miRNAs had a total of 2,414 predicted circRNA interactions with 16 miRNAs having over 200 circRNA interactions ( Figure 8D ). Relative to the Ascaris miRNAs that were predicted to frequently bind to Ascaris circRNAs, more functional information is known about these human miRNAs that are predicted to bind to Ascaris circRNAs, among them hsa-miR-4668-5p, which had the highest number of predicted circRNA interactions at 291. hsa-miR-4668-5p has been implicated in regulating TGF-beta signaling ( Bhardwaj et al, 2020 ). TGF-beta is a cytokine involved in the proliferation, differentiation and function of lymphocytes, macrophages, and dendritic cells ( Kubiczkova et al, 2012 ) and dysregulation of TGF-beta through circRNA sponging could potentially be another strategy these parasitic worms use to manipulate and modulate the host immune response.…”

Preclinical Studies on Convalescent Human Immune Plasma-Derived Exosome: Omics and Antiviral Properties to SARS-CoV-2

“…When these 16 pathways are examined in detail, they overlap with the definitions of miRNAs found in the literature ( 41 ). Overall, the common theme of the miRNA profile of ChipEXO appears to center on those promoting tropism and those involved in immune regulation, most already defined in the literature ( 42 , 43 ). Interestingly, two miRNAs, mir-3613-3p and mir-635, found in ChipEXO are known to inhibit type I interferon pathway ( 44 ) possibly by mechanisms involving cytidine monophosphate kinase 1 (CMPK1) as well as JAK kinases (JAK1 and JAK3) ( 45 ).…”

Micro RNAs as potential biomarkers in tuberculosis: A systematic review

“…Bioinformatics analysis of miR-4484 suggests that the microRNA targets TGF-β and other Wnt/β-catenin signalling pathway-associated genes regulates apoptosis and is involved in collagen regulation related genes [ 79 ]. Another miRNA, miR-4668-5p, also targets TGF-β pathway-related genes and is involved in allergic diseases [ 80 ]. Other reports suggest that miR-144 expresses in T cells of active tuberculosis patients [ 81 ].…”