000143225 001__ 143225
000143225 005__ 20240229112545.0
000143225 0247_ $$2doi$$a10.1038/s41598-019-40857-3
000143225 0247_ $$2pmid$$apmid:30886199
000143225 0247_ $$2pmc$$apmc:PMC6423323
000143225 037__ $$aDKFZ-2019-00824
000143225 041__ $$aeng
000143225 082__ $$a600
000143225 1001_ $$aGoeppert, Benjamin$$b0
000143225 245__ $$aProfiling of gallbladder carcinoma reveals distinct miRNA profiles and activation of STAT1 by the tumor suppressive miRNA-145-5p.
000143225 260__ $$a[London]$$bMacmillan Publishers Limited, part of Springer Nature$$c2019
000143225 3367_ $$2DRIVER$$aarticle
000143225 3367_ $$2DataCite$$aOutput Types/Journal article
000143225 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1613569044_15338
000143225 3367_ $$2BibTeX$$aARTICLE
000143225 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000143225 3367_ $$00$$2EndNote$$aJournal Article
000143225 520__ $$aGallbladder carcinoma (GBC) is a biliary tract cancer with few treatment options and poor prognosis. Radical surgery is the only potentially curative treatment option but most patients diagnosed with GBC are unresectable. Thus, there is a great need for the development of new treatment options including targeted therapy. Here, we aimed at identifying deregulated miRNAs and affected pathways involved in GBC development and progression. We performed global miRNA profiling of 40 GBC and 8 normal gallbladder tissues and identified large differences with 30% of miRNAs being differentially expressed (false discovery rate: FDR < 0.001). We found 24 miRNAs to be differentially regulated in GBC with poor outcome (p < 0.05) of which miR-145-5p was the most downregulated miRNA. Overexpression of miR-145-5p significantly reduced cell proliferation and colony formation. Gene expression analysis of cells expressing miR-145-5p mimics revealed activation of the Signal transducer and activator of transcription 1 (STAT1) signaling pathway which is mainly tumor suppressive. Furthermore, the activation of STAT1 by miR-145-5p was specifically observed in gallbladder carcinoma and cholangiocarcinoma but not in hepatocellular carcinoma cells. The Protein Tyrosine Phosphatase Receptor Type F (PTPRF) is downregulated upon miR-145 expression and may be involved in STAT1 regulation. In addition, we found that the STAT1-regulated protein IRF7 is downregulated in GBC compared to normal gallbladder tissue and low IRF7 expression is associated with significantly lower overall survival of GBC patients. Thus, this study identified GBC patient subgroups and provides new mechanistic insights in the tumor suppressive function of miR-145-5p leading to activation of STAT1 signaling.
000143225 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0
000143225 588__ $$aDataset connected to CrossRef, PubMed,
000143225 7001_ $$aTruckenmueller, Felicia$$b1
000143225 7001_ $$aOri, Alessandro$$b2
000143225 7001_ $$aFritz, Valerie$$b3
000143225 7001_ $$aAlbrecht, Thomas$$b4
000143225 7001_ $$aFraas, Angelika$$b5
000143225 7001_ $$aScherer, Dominique$$b6
000143225 7001_ $$aSilos, Rosa González$$b7
000143225 7001_ $$aSticht, Carsten$$b8
000143225 7001_ $$aGretz, Norbert$$b9
000143225 7001_ $$aMehrabi, Arianeb$$b10
000143225 7001_ $$0P:(DE-He78)7999346780553d7fab7ba69d5afdfa71$$aBewerunge-Hudler, Melanie$$b11$$udkfz
000143225 7001_ $$0P:(DE-He78)f2efee17b6ca2f790176a2c036912536$$aPusch, Stefan$$b12$$udkfz
000143225 7001_ $$aBermejo, Justo Lorenzo$$b13
000143225 7001_ $$aDietrich, Peter$$b14
000143225 7001_ $$aSchirmacher, Peter$$b15
000143225 7001_ $$aRenner, Marcus$$b16
000143225 7001_ $$00000-0002-5333-5942$$aRoessler, Stephanie$$b17
000143225 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/s41598-019-40857-3$$gVol. 9, no. 1, p. 4796$$n1$$p4796$$tScientific reports$$v9$$x2045-2322$$y2019
000143225 909CO $$ooai:inrepo02.dkfz.de:143225$$pVDB
000143225 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)7999346780553d7fab7ba69d5afdfa71$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ
000143225 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f2efee17b6ca2f790176a2c036912536$$aDeutsches Krebsforschungszentrum$$b12$$kDKFZ
000143225 9131_ $$0G:(DE-HGF)POF3-312$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunctional and structural genomics$$x0
000143225 9141_ $$y2019
000143225 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bSCI REP-UK : 2017
000143225 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000143225 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000143225 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000143225 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central
000143225 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal
000143225 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ
000143225 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review
000143225 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ
000143225 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000143225 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000143225 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000143225 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000143225 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000143225 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000143225 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences
000143225 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record
000143225 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000143225 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000143225 9201_ $$0I:(DE-He78)W110-20160331$$kW110$$lW110 Microarray Unit$$x0
000143225 9201_ $$0I:(DE-He78)B300-20160331$$kB300$$lKKE Neuropathologie$$x1
000143225 980__ $$ajournal
000143225 980__ $$aVDB
000143225 980__ $$aI:(DE-He78)W110-20160331
000143225 980__ $$aI:(DE-He78)B300-20160331
000143225 980__ $$aUNRESTRICTED