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

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: Tan, I L, Barisani, D, Panceri, R, Modderman, R, Visschedijk, M, Weersma, R K, Wijmenga, C, Jonkers, I, Coutinho de Almeida, R & Withoff, S 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, vol. 22, no. 21, 11382. https://doi.org/10.3390/ijms222111382
Publication Year: 2021
Collection: University of Groningen research database
Description: 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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
ISSN: 1422-0067
Relation: info:eu-repo/semantics/altIdentifier/pmid/34768815; info:eu-repo/semantics/altIdentifier/hdl/https://hdl.handle.net/11370/5ac2ebfd-3645-4af3-bf58-e382cfffe4c9; info:eu-repo/semantics/altIdentifier/pissn/1422-0067
DOI: 10.3390/ijms222111382
Availability: https://hdl.handle.net/11370/5ac2ebfd-3645-4af3-bf58-e382cfffe4c9; https://research.rug.nl/en/publications/5ac2ebfd-3645-4af3-bf58-e382cfffe4c9; https://doi.org/10.3390/ijms222111382; https://pure.rug.nl/ws/files/193718956/ijms_22_11382_v3.pdf
Rights: info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.FF9B13D4
Database: BASE