MiR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Wohlfarth, Carolin; Schmitteckert, Stefanie; Härtle, Janina; Houghton, Lesley; Dweep, Harsh; Fortea, Marina; Assadi, Ghazaleh; Braun, Alexander; Mederer, Tanja; Pöhner, Sarina; Becker, Philip; Fischer, Christine; Granzow, Martin; Mönnikes, Hubert; Mayer, Emeran; Sayuk, Gregory; Boeckxstaens, Guy; Wouters, Mira; Simrén, Magnus; Lindberg, Greger; Ohlsson, Bodil; Schmidt, Peter; Dlugosz, Aldona; Agreus, Lars; Andreasson, Anna; D'Amato, Mauro; Burwinkel, Barbara; Bermejo, Justo; Röth, Ralph; Lasitschka, Felix; Vicario, Maria; Metzger, Marco; Santos, Javier; Rappold, Gudrun; Martinez, Cristina; Niesler, Beate;
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 14
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-13982-0
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT4 R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT4 receptor geneHTR4 to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoformsHTR4b/i and putatively impairsHTR4 expression. Subsequent miRNA-profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms.In vitro assays confirmed expression regulation via three 3′UTR binding sites. The novel isoformHTR4b_2 lacking two of the three miRNA binding sites escapes miR-16/103/107 regulation in SNP carriers. We provide the first evidence thatHTR4 expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or by diminished levels of miR-16 and miR-103 suggesting thatHTR4 might be involved in the development of IBS-D.