@article{WohlfarthSchmitteckertHaertleetal.2017,
  author    = {Wohlfarth, Carolin and Schmitteckert, Stefanie and H{\"a}rtle, Janina D. and Houghton, Lesley A. and Dweep, Harsh and Fortea, Marina and Assadi, Ghazaleh and Braun, Alexander and Mederer, Tanja and P{\"o}hner, Sarina and Becker, Philip P. and Fischer, Christine and Granzow, Martin and M{\"o}nnikes, Hubert and Mayer, Emeran A. and Sayuk, Gregory and Boeckxstaens, Guy and Wouters, Mira M. and Simr{\´e}n, Magnus and Lindberg, Greger and Ohlsson, Bodil and Schmidt, Peter Thelin and Dlugosz, Aldona and Agreus, Lars and Andreasson, Anna and D'Amato, Mauro and Burwinkel, Barbara and Bermejo, Justo Lorenzo and R{\"o}th, Ralph and Lasitschka, Felix and Vicario, Maria and Metzger, Marco and Santos, Javier and Rappold, Gudrun A. and Martinez, Cristina and Niesler, Beate},
  title     = {miR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-017-13982-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173478},
  year      = {2017},
  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-HT4R 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 gene \(HTR4\) 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 isoforms \({HTR4b/i}\) and putatively impairs \(HTR4\) 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 isoform \(HTR4b\_2\) lacking two of the three miRNA binding sites escapes miR-16/103/107 regulationin SNP carriers. We provide the first evidence that \(HTR4\) expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or bydiminished levels of miR-16 and miR-103 suggesting that \(HTR4\) might be involved in the development of IBS-D.},
  language  = {en}
}
@article{BeckerRauSchmittetal.2015,
  author    = {Becker, Philip P. and Rau, Monika and Schmitt, Johannes and Malsch, Carolin and Hammer, Christian and Bantel, Heike and M{\"u}llhaupt, Beat and Geier, Andreas},
  title     = {Performance of serum microRNAs -122, -192 and -21 as biomarkers in patients with non-alcoholic steatohepatitis},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {11},
  doi       = {10.1371/journal.pone.0142661},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145147},
  pages     = {e0142661},
  year      = {2015},
  abstract  = {Objectives Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH) diagnosis. Their invasive nature, however, still carries an increased risk for patients' health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL) and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers. Methods Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH. Results The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001). Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95\% CI = 0.754-0.908; p<0.001). Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91\%) and specificity (83\%). Conclusions Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.},
  language  = {en}
}