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Status: Bibliographieeintrag

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Verfasst von:Goeppert, Benjamin [VerfasserIn]   i
 Truckenmüller, Felicia [VerfasserIn]   i
 Albrecht, Thomas [VerfasserIn]   i
 Fraas, Angelika [VerfasserIn]   i
 Scherer, Dominique [VerfasserIn]   i
 González Silos, Rosa [VerfasserIn]   i
 Mehrabi, Arianeb [VerfasserIn]   i
 Pusch, Stefan [VerfasserIn]   i
 Lorenzo Bermejo, Justo [VerfasserIn]   i
 Schirmacher, Peter [VerfasserIn]   i
 Renner, Marcus [VerfasserIn]   i
 Rössler, Stephanie [VerfasserIn]   i
Titel:Profiling of gallbladder carcinoma reveals distinct miRNA profiles and activation of STAT1 by the tumor suppressive miRNA-145-5p
Verf.angabe:Benjamin Goeppert, Felicia Truckenmueller, Alessandro Ori, Valerie Fritz, Thomas Albrecht, Angelika Fraas, Dominique Scherer, Rosa González Silos, Carsten Sticht, Norbert Gretz, Arianeb Mehrabi, Melanie Bewerunge-Hudler, Stefan Pusch, Justo Lorenzo Bermejo, Peter Dietrich, Peter Schirmacher, Marcus Renner and Stephanie Roessler
E-Jahr:2019
Jahr:18 March 2019
Umfang:13 S.
Fussnoten:Gesehen am 05.04.2019
Titel Quelle:Enthalten in: Scientific reports
Ort Quelle:[London] : Macmillan Publishers Limited, part of Springer Nature, 2011
Jahr Quelle:2019
Band/Heft Quelle:9(2019) Artikel-Nummer 4796, 13 Seiten
ISSN Quelle:2045-2322
Abstract:Gallbladder carcinoma (GBC) is a biliary tract cancer with few treatment options and poor prognosis. Radical surgery is the only potentially curative treatment option but most patients diagnosed with GBC are unresectable. Thus, there is a great need for the development of new treatment options including targeted therapy. Here, we aimed at identifying deregulated miRNAs and affected pathways involved in GBC development and progression. We performed global miRNA profiling of 40 GBC and 8 normal gallbladder tissues and identified large differences with 30% of miRNAs being differentially expressed (false discovery rate: FDR < 0.001). We found 24 miRNAs to be differentially regulated in GBC with poor outcome (p < 0.05) of which miR-145-5p was the most downregulated miRNA. Overexpression of miR-145-5p significantly reduced cell proliferation and colony formation. Gene expression analysis of cells expressing miR-145-5p mimics revealed activation of the Signal transducer and activator of transcription 1 (STAT1) signaling pathway which is mainly tumor suppressive. Furthermore, the activation of STAT1 by miR-145-5p was specifically observed in gallbladder carcinoma and cholangiocarcinoma but not in hepatocellular carcinoma cells. The Protein Tyrosine Phosphatase Receptor Type F (PTPRF) is downregulated upon miR-145 expression and may be involved in STAT1 regulation. In addition, we found that the STAT1-regulated protein IRF7 is downregulated in GBC compared to normal gallbladder tissue and low IRF7 expression is associated with significantly lower overall survival of GBC patients. Thus, this study identified GBC patient subgroups and provides new mechanistic insights in the tumor suppressive function of miR-145-5p leading to activation of STAT1 signaling.
DOI:doi:10.1038/s41598-019-40857-3
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1038/s41598-019-40857-3
 Volltext: https://www.nature.com/articles/s41598-019-40857-3
 DOI: https://doi.org/10.1038/s41598-019-40857-3
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1662884125
Verknüpfungen:→ Zeitschrift

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