| Title: |
A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease. |
| Authors: |
Tan, Ineke Luise, Barisani, Donatella, Panceri, Roberto, Modderman, Rutger, Visschedijk, Marijn, Weersma, Rinse K., Wijmenga, Cisca, Jonkers, Iris, Coutinho de Almeida, Rodrigo, Withoff, Sebo |
| Source: |
International Journal of Molecular Sciences; Nov2021, Vol. 22 Issue 21, p11382, 1p |
| Subject Terms: |
TRANSCRIPTOMES, MICRORNA, CELIAC disease, INTESTINES, SMALL intestine, GLUTEN |
| 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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