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.

Tan, I., Barisani, D., Panceri, R., Modderman, R., Visschedij, M., Weersma, R., et al. (2021). A combined mRNA- and miRNA-sequencing approach reveals miRNAs as potential regulators of the small intestinal transcriptome in celiac disease. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(21) [10.3390/ijms222111382].

A combined mRNA- and miRNA-sequencing approach reveals miRNAs as potential regulators of the small intestinal transcriptome in celiac disease

Barisani D.;
2021

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.
Articolo in rivista - Articolo scientifico
Autoimmunity; MiRNA‒target gene regulation; Post-translational transcript regulation;
English
21-ott-2021
2021
22
21
11382
none
Tan, I., Barisani, D., Panceri, R., Modderman, R., Visschedij, M., Weersma, R., et al. (2021). A combined mRNA- and miRNA-sequencing approach reveals miRNAs as potential regulators of the small intestinal transcriptome in celiac disease. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(21) [10.3390/ijms222111382].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/333426
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