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@ARTICLE{Goeppert:143225,
author = {B. Goeppert and F. Truckenmueller and A. Ori and V. Fritz
and T. Albrecht and A. Fraas and D. Scherer and R. G. Silos
and C. Sticht and N. Gretz and A. Mehrabi and M.
Bewerunge-Hudler$^*$ and S. Pusch$^*$ and J. L. Bermejo and
P. Dietrich and P. Schirmacher and M. Renner and S.
Roessler},
title = {{P}rofiling of gallbladder carcinoma reveals distinct
mi{RNA} profiles and activation of {STAT}1 by the tumor
suppressive mi{RNA}-145-5p.},
journal = {Scientific reports},
volume = {9},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {DKFZ-2019-00824},
pages = {4796},
year = {2019},
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.},
cin = {W110 / B300},
ddc = {600},
cid = {I:(DE-He78)W110-20160331 / I:(DE-He78)B300-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30886199},
pmc = {pmc:PMC6423323},
doi = {10.1038/s41598-019-40857-3},
url = {https://inrepo02.dkfz.de/record/143225},
}