NOD2 Is Regulated by MIR-320 in Physiological Conditions but this Control Is Altered in Inflamed Tissues of Patients with Inflammatory Bowel Disease

Maria Pierdomenico, Vincenzo Cesi, Salvatore Cucchiara, Roberta Vitali, Enrica Prete, Manuela Costanzo, Marina Aloi, Salvatore Oliva, Laura Stronati

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19 Citations (Scopus)

Abstract

Background: Large evidence supports the role of microRNAs as new important inflammatory mediators by regulating both the adaptive and innate immunity. In the present study, we speculated that miR-320 controls NOD2 (nucleotide-binding oligomerization domain) expression, because it contains multiple binding sites in the 3′-untranslated region of the gene. NOD2, the first gene associated to increased susceptibility to Crohn's disease, is a cytosolic receptor that senses wall peptides of bacteria and promotes their clearance through initiation of a proinflammatory transcriptional program. This study aims at demonstrating that NOD2 is a target of miR-320 as well as investigating the role of inflammation in modulating the miR-320 control on NOD2 expression and analyzing miR-320 expression in intestinal biopsies of children with inflammatory bowel disease. Methods: The colonic adenocarcinoma cell line HT29 was used to assess the miR-320-mediated regulation of NOD2 expression. MiR-320 and NOD2 expression were analyzed in mucosal samples of 40 children with inflammatory bowel disease. Results: During inflammation, NOD2 expression is inversely correlated with miR-320 expression in vitro and ex vivo. Exogenous miR-320 transfection in HT29 cells leads to a significant decrease of NOD2 expression, whereas the miR-320 inhibitor transfection leads to increase of NOD2 expression, nuclear translocation of nuclear factor B, and activation of downstream cytokines. Conclusions: We show for the first time that NOD2 expression is under the control of miR-320. We also show in vitro and ex vivo that inflammation induces a decrease of miR-320 and the latter correlates negatively with NOD2 expression.
Original languageEnglish
Pages (from-to)315 - 326
Number of pages12
JournalInflammatory Bowel Diseases
Volume22
Issue number2
DOIs
Publication statusPublished - 11 Jan 2016
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

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