Profiling of gallbladder carcinoma reveals distinct miRNA profiles and activation of STAT1 by the tumor suppressive miRNA-145-5p

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Goeppert B, Truckenmueller F, Ori A, Fritz V, Albrecht T, Fraas A, Scherer D, Silos RG, Sticht C, Gretz N, Mehrabi A, Bewerunge-Hudler M, Pusch S, Bermejo JL, Dietrich P, Schirmacher P, Renner M, Roessler S
Zeitschrift: Scientific Reports
Jahr der Veröffentlichung: 2019
Band: 9
ISSN: 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.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Dietrich, Peter Dr.
Lehrstuhl für Biochemie und Molekulare Medizin
Fritz, Valerie
Lehrstuhl für Biochemie und Molekulare Medizin


Einrichtungen weiterer Autorinnen und Autoren

Deutsches Krebsforschungszentrum (DKFZ)
Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut (FLI)
Universitätsklinikum Heidelberg
Universitätsklinikum Mannheim


Zitierweisen

APA:
Goeppert, B., Truckenmueller, F., Ori, A., Fritz, V., Albrecht, T., Fraas, A.,... Roessler, S. (2019). Profiling of gallbladder carcinoma reveals distinct miRNA profiles and activation of STAT1 by the tumor suppressive miRNA-145-5p. Scientific Reports, 9. https://dx.doi.org/10.1038/s41598-019-40857-3

MLA:
Goeppert, Benjamin, et al. "Profiling of gallbladder carcinoma reveals distinct miRNA profiles and activation of STAT1 by the tumor suppressive miRNA-145-5p." Scientific Reports 9 (2019).

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Zuletzt aktualisiert 2019-29-03 um 21:08