A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease

Abstract

Celiac disease (CeD) is triggered by gluten and results in inflammation and villous atrophy of the small intestine. We aimed to explore the role of miRNA-mediated deregulation of the transcriptome in CeD. Duodenal biopsies of CeD patients (n = 33) and control subjects (n = 10) were available for miRNA-sequencing, with RNA-sequencing also available for controls (n = 5) and CeD (n = 6). Differential expression analysis was performed to select CeD-associated miRNAs and genes. MiRNA‒target transcript pairs selected from public databases that also displayed a strong negative expression correlation in the current dataset (R < −0.7) were used to construct a CeD miRNA‒target transcript interaction network. The network includes 2030 miRNA‒target transcript interactions, including 423 experimentally validated pairs. Pathway analysis found that interactions are involved in immune-related pathways (e.g., interferon signaling) and metabolic pathways (e.g., lipid metabolism). The network includes 13 genes previously prioritized to be causally deregulated by CeD-associated genomic variants, including STAT1. CeD-associated miRNAs might play a role in promoting inflammation and decreasing lipid metabolism in the small intestine, thereby contributing unbalanced cell turnover in the intestinal crypt. Some CeD-associated miRNAs deregulate genes that are also affected by genomic CeD-risk variants, adding an additional layer of complexity to the deregulated transcriptome in CeD.

Novel Bacteroides Vulgatus strain protects against gluten-induced break of human celiac gut epithelial homeostasis: a pre-clinical proof-of-concept study

“…Specifically, we have shown that organoid-derived monolayers from PCeD downregulated the expression of miR-15a-5p, miR-145-5p, miR146a-5p, and miR-223-3p after treatment with B. vulgatus -A2 CFS. These data are in accordance with the previous literature, 37 – 39 except for miR-145-5p for which a reduced expression was reported in CeD patients. 40 Target prediction and gene set enrichment analyses linked the four miRNAs to signaling pathways, which have been previously shown to be involved in CeD pathogenesis.…”

Potential biomarkers for multiple sclerosis stage from targeted proteomics and microRNA sequencing

“…To get insights into the cell types that might contribute to the differences in the extracellular miRNA profiles between different subgroups, we calculated cell type–enrichment scores from miRNA data. 21 This approach uses the observation that miRNA profiles are highly variable between cell types. 22 , 23 The top 10 miRNAs expressed in immune and neurological cell types were extracted from the miRNA atlas described by De Rie et al .…”

Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells From Pediatric Coeliac Disease Patients Suggests Potential Pre-Seroconversion Markers

“…There are two types of RNA markers in blood: circulating ‘cell-free’ RNA (e.g. miRNAs or other RNA species that might be present in vesicles) and cellular/PBMC RNA ( 14 ). However, most studies that try to identify cellular RNA markers in blood rely on the analysis of mixed PBMC populations.…”