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winkler-et-al-2019-identification-of-pparγ-modulated-mirna-hubs-that-target-the-fibrotic-tumor-microenvironment.pdf 1,74MB
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1000 Titel
  • Identification of Ppar <i>γ</i> -modulated miRNA hubs that target the fibrotic tumor microenvironment
1000 Autor/in
  1. Winkler, Ivana |
  2. Bitter, Catrin |
  3. Winkler, Sebastian |
  4. Weichenhan, Dieter |
  5. Thavamani, Abhishek |
  6. Hengstler, Jan G. |
  7. Borkham-Kamphorst, Erawan |
  8. Kohlbacher, Oliver |
  9. Plass, Christoph |
  10. Geffers, Robert |
  11. Weiskirchen, Ralf |
  12. Nordheim, Alfred |
1000 Erscheinungsjahr 2020
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2019-12-23
1000 Erschienen in
1000 Quellenangabe
  • 117(1):454-463
1000 FRL-Sammlung
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1073/pnas.1909145117 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955372/ |
1000 Ergänzendes Material
  • https://www.pnas.org/doi/full/10.1073/pnas.1909145117#supplementary-materials |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Liver 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.
1000 Sacherschließung
lokal Extracellular Matrix/pathology [MeSH]
lokal PPAR gamma/metabolism [MeSH]
lokal Carcinoma, Hepatocellular/pathology
lokal Liver/pathology [MeSH]
lokal Lung Neoplasms/genetics [MeSH]
lokal Epigenesis, Genetic
lokal Breast Neoplasms/pathology
lokal Lung Neoplasms/genetics
lokal Carcinoma, Hepatocellular/genetics
lokal Liver Cirrhosis/pathology [MeSH]
lokal Extracellular Matrix/pathology
lokal Liver/cytology [MeSH]
lokal Liver/pathology
lokal MicroRNAs/genetics [MeSH]
lokal Disease Models, Animal [MeSH]
lokal Female [MeSH]
lokal DNA Methylation
lokal Humans [MeSH]
lokal Breast Neoplasms/genetics [MeSH]
lokal Lung Neoplasms/pathology
lokal CpG Islands/genetics
lokal Animals [MeSH]
lokal Gene Expression Regulation, Neoplastic
lokal Disease Models, Animal
lokal Datasets as Topic
lokal CpG Islands/genetics [MeSH]
lokal Liver/cytology
lokal Lung Neoplasms/pathology [MeSH]
lokal Promoter Regions, Genetic/genetics
lokal Hepatic Stellate Cells/pathology
lokal MicroRNAs/genetics
lokal Tumor Microenvironment/genetics [MeSH]
lokal Gene Expression Regulation, Neoplastic [MeSH]
lokal Breast Neoplasms/genetics
lokal Liver Neoplasms/genetics
lokal Tumor Microenvironment/genetics
lokal Female
lokal Liver Cirrhosis/pathology
lokal Mice
lokal Liver Neoplasms/pathology [MeSH]
lokal RNA-Seq [MeSH]
lokal Primary Cell Culture [MeSH]
lokal Liver Neoplasms/genetics [MeSH]
lokal Breast Neoplasms/pathology [MeSH]
lokal Liver Neoplasms/pathology
lokal Humans
lokal PPAR gamma/metabolism
lokal Datasets as Topic [MeSH]
lokal RNA-Seq
lokal Carcinoma, Hepatocellular/pathology [MeSH]
lokal Epigenesis, Genetic [MeSH]
lokal Promoter Regions, Genetic/genetics [MeSH]
lokal Mice [MeSH]
lokal Carcinoma, Hepatocellular/genetics [MeSH]
lokal DNA Methylation [MeSH]
lokal Hepatic Stellate Cells/pathology [MeSH]
lokal Animals
lokal Primary Cell Culture
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/V2lua2xlciwgSXZhbmE=|https://frl.publisso.de/adhoc/uri/Qml0dGVyLCBDYXRyaW4=|https://frl.publisso.de/adhoc/uri/V2lua2xlciwgU2ViYXN0aWFu|https://frl.publisso.de/adhoc/uri/V2VpY2hlbmhhbiwgRGlldGVy|https://frl.publisso.de/adhoc/uri/VGhhdmFtYW5pLCBBYmhpc2hlaw==|https://frl.publisso.de/adhoc/uri/SGVuZ3N0bGVyLCBKYW4gRy4=|https://frl.publisso.de/adhoc/uri/Qm9ya2hhbS1LYW1waG9yc3QsIEVyYXdhbg==|https://orcid.org/0000-0003-1739-4598|https://frl.publisso.de/adhoc/uri/UGxhc3MsIENocmlzdG9waA==|https://frl.publisso.de/adhoc/uri/R2VmZmVycywgUm9iZXJ0|https://orcid.org/0000-0003-3888-0931|https://frl.publisso.de/adhoc/uri/Tm9yZGhlaW0sIEFsZnJlZA==
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1000 Fördernummer
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  1. Identification of Ppar <i>γ</i> -modulated miRNA hubs that target the fibrotic tumor microenvironment
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1000 Erstellt am 2024-05-08T09:53:22.518+0200
1000 Erstellt von 336
1000 beschreibt frl:6475678
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet 2024-05-27T09:42:56.243+0200
1000 Objekt bearb. Mon May 27 09:42:44 CEST 2024
1000 Vgl. frl:6475678
1000 Oai Id
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