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

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 (<i>n</i> = 33) and control subjects (<i>n&...

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Autores principales:	Ineke Luise Tan, Donatella Barisani, Roberto Panceri, Rutger Modderman, Marijn Visschedijk, Rinse K. Weersma, Cisca Wijmenga, Iris Jonkers, Rodrigo Coutinho de Almeida, Sebo Withoff
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	miRNA‒target gene regulation post-translational transcript regulation autoimmunity Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/9518fc1809934dfdae24a9c0c20d598d
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spelling	oai:doaj.org-article:9518fc1809934dfdae24a9c0c20d598d2021-11-11T16:51:30ZA Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease10.3390/ijms2221113821422-00671661-6596https://doaj.org/article/9518fc1809934dfdae24a9c0c20d598d2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11382https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Celiac 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 (<i>n</i> = 33) and control subjects (<i>n</i> = 10) were available for miRNA-sequencing, with RNA-sequencing also available for controls (<i>n</i> = 5) and CeD (<i>n</i> = 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.Ineke Luise TanDonatella BarisaniRoberto PanceriRutger ModdermanMarijn VisschedijkRinse K. WeersmaCisca WijmengaIris JonkersRodrigo Coutinho de AlmeidaSebo WithoffMDPI AGarticlemiRNA‒target gene regulationpost-translational transcript regulationautoimmunityBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11382, p 11382 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	miRNA‒target gene regulation post-translational transcript regulation autoimmunity Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	miRNA‒target gene regulation post-translational transcript regulation autoimmunity Biology (General) QH301-705.5 Chemistry QD1-999 Ineke Luise Tan Donatella Barisani Roberto Panceri Rutger Modderman Marijn Visschedijk Rinse K. Weersma Cisca Wijmenga Iris Jonkers Rodrigo Coutinho de Almeida Sebo Withoff A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease
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 (<i>n</i> = 33) and control subjects (<i>n</i> = 10) were available for miRNA-sequencing, with RNA-sequencing also available for controls (<i>n</i> = 5) and CeD (<i>n</i> = 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.
format	article
author	Ineke Luise Tan Donatella Barisani Roberto Panceri Rutger Modderman Marijn Visschedijk Rinse K. Weersma Cisca Wijmenga Iris Jonkers Rodrigo Coutinho de Almeida Sebo Withoff
author_facet	Ineke Luise Tan Donatella Barisani Roberto Panceri Rutger Modderman Marijn Visschedijk Rinse K. Weersma Cisca Wijmenga Iris Jonkers Rodrigo Coutinho de Almeida Sebo Withoff
author_sort	Ineke Luise Tan
title	A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease
title_short	A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease
title_full	A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease
title_fullStr	A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease
title_full_unstemmed	A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease
title_sort	combined mrna- and mirna-sequencing approach reveals mirnas as potential regulators of the small intestinal transcriptome in celiac disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9518fc1809934dfdae24a9c0c20d598d
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A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease

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