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dc.contributor.authorWinkler, Ivana
dc.contributor.authorBitter, Catrin
dc.contributor.authorWinkler, Sebastian
dc.contributor.authorWeichenhan, Dieter
dc.contributor.authorThavamani, Abhishek
dc.contributor.authorHengstler, Jan G
dc.contributor.authorBorkham-Kamphorst, Erawan
dc.contributor.authorKohlbacher, Oliver
dc.contributor.authorPlass, Christoph
dc.contributor.authorGeffers, Robert
dc.contributor.authorWeiskirchen, Ralf
dc.contributor.authorNordheim, Alfred
dc.date.accessioned2020-01-14T13:38:12Z
dc.date.available2020-01-14T13:38:12Z
dc.date.issued2020-01-07
dc.identifier.citationProc Natl Acad Sci U S A. 2020 Jan 7;117(1):454-463. doi: 10.1073/pnas.1909145117. Epub 2019 Dec 23.en_US
dc.identifier.issn1091-6490
dc.identifier.pmid31871210
dc.identifier.doi10.1073/pnas.1909145117
dc.identifier.urihttp://hdl.handle.net/10033/622079
dc.description.abstractLiver fibrosis interferes with normal liver function and facilitates hepatocellular carcinoma (HCC) development, representing a major threat to human health. Here, we present a comprehensive perspective of microRNA (miRNA) function on targeting the fibrotic microenvironment. Starting from a murine HCC model, we identify a miRNA network composed of 8 miRNA hubs and 54 target genes. We show that let-7, miR-30, miR-29c, miR-335, and miR-338 (collectively termed antifibrotic microRNAs [AF-miRNAs]) down-regulate key structural, signaling, and remodeling components of the extracellular matrix. During fibrogenic transition, these miRNAs are transcriptionally regulated by the transcription factor Pparγ and thus we identify a role of Pparγ as regulator of a functionally related class of AF-miRNAs. The miRNA network is active in human HCC, breast, and lung carcinomas, as well as in 2 independent mouse liver fibrosis models. Therefore, we identify a miRNA:mRNA network that contributes to formation of fibrosis in tumorous and nontumorous organs of mice and humans.en_US
dc.publisherNational Academy of Sciencesen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectPPARγen_US
dc.subjectfibrosisen_US
dc.subjecthepatocellular carcinomaen_US
dc.subjectmicroRNAsen_US
dc.titleIdentification of Ppar-modulated miRNA hubs that target the fibrotic tumor microenvironment.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalProceedings of the National Academy of sciencesen_US
refterms.dateFOA2020-01-14T13:38:13Z
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America


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