| |  Online-Ressource |
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| Verfasst von: | Goeppert, Benjamin [VerfasserIn]  |
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| | Ernst, Christina [VerfasserIn] |
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| | Baer, Constance [VerfasserIn] |
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| | Rössler, Stephanie [VerfasserIn] |
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| | Renner, Marcus [VerfasserIn] |
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| | Mehrabi, Arianeb [VerfasserIn] |
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| | Hafezi, Mohammadreza [VerfasserIn] |
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| | Pathil-Warth, Anita [VerfasserIn] |
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| | Warth, Arne [VerfasserIn] |
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| | Stenzinger, Albrecht [VerfasserIn] |
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| | Weichert, Wilko [VerfasserIn] |
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| | Bähr, Marion [VerfasserIn] |
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| | Will, Rainer [VerfasserIn] |
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| | Schirmacher, Peter [VerfasserIn] |
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| | Plass, Christoph [VerfasserIn] |
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| | Weichenhan, Dieter [VerfasserIn] |
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| Titel: | Cadherin-6 is a putative tumor suppressor and target of epigenetically dysregulated miR-429 in cholangiocarcinoma |
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| Verf.angabe: | Benjamin Goeppert, Christina Ernst, Constance Baer, Stephanie Roessler, Marcus Renner, Arianeb Mehrabi, Mohammadreza Hafezi, Anita Pathil, Arne Warth, Albrecht Stenzinger, Wilko Weichert, Marion Bähr, Rainer Will, Peter Schirmacher, Christoph Plass, and Dieter Weichenhan |
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| E-Jahr: | 2016 |
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| Jahr: | 18 August 2016 |
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| Umfang: | 11 S. |
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| Fussnoten: | Gesehen am 24.06.2020 |
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| Titel Quelle: | Enthalten in: Epigenetics |
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| Ort Quelle: | Austin, Tex. : Landes Bioscience, 2006 |
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| Jahr Quelle: | 2016 |
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| Band/Heft Quelle: | 11(2016), 11, Seite 780-790 |
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| ISSN Quelle: | 1559-2308 |
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| Abstract: | Cholangiocarcinoma (CC) is a rare malignancy of the extrahepatic or intrahepatic biliary tract with an outstanding poor prognosis. Non-surgical therapeutic regimens result in minimally improved survival of CC patients. Global genomic analyses identified a few recurrently mutated genes, some of them in genes involved in epigenetic patterning. In a previous study, we demonstrated global DNA methylation changes in CC, indicating major contribution of epigenetic alterations to cholangiocarcinogenesis. Here, we aimed at the identification and characterization of CC-related, differentially methylated regions (DMRs) in potential microRNA promoters and of genes targeted by identified microRNAs. Twenty-seven hypermethylated and 13 hypomethylated potential promoter regions of microRNAs, known to be associated with cancer-related pathways like Wnt, ErbB, and PI3K-Akt signaling, were identified. Selected DMRs were confirmed in 2 independent patient cohorts. Inverse correlation between promoter methylation and expression suggested miR-129-2 and members of the miR-200 family (miR-200a, miR-200b, and miR-429) as novel tumor suppressors and oncomiRs, respectively, in CC. Tumor suppressor genes deleted in liver cancer 1 (DLC1), F-box/WD-repeat-containing protein 7 (FBXW7), and cadherin-6 (CDH6) were identified as presumed targets in CC. Tissue microarrays of a representative and well-characterized cohort of biliary tract cancers (n=212) displayed stepwise downregulation of CDH6 and association with poor patient outcome. Ectopic expression of CDH6 on the other hand, delayed growth in the CC cell lines EGI-1 and TFK-1, together suggesting a tumor suppressive function of CDH6. Our work represents a valuable repository for the study of epigenetically altered miRNAs in cholangiocarcinogenesis and novel putative, CC-related tumor suppressive miRNAs and oncomiRs. |
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| DOI: | doi:10.1080/15592294.2016.1227899 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
DOI: https://doi.org/10.1080/15592294.2016.1227899 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Adult |
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| | Aged |
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| | Aged, 80 and over |
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| | Biliary tract cancer |
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| | Cadherins |
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| | Cell Cycle Proteins |
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| | Cell Line, Tumor |
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| | Cholangiocarcinoma |
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| | DNA methylation |
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| | DNA Methylation |
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| | Epigenesis, Genetic |
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| | epigenomics |
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| | F-Box Proteins |
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| | F-Box-WD Repeat-Containing Protein 7 |
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| | Female |
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| | Gene Expression Regulation, Neoplastic |
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| | GTPase-Activating Proteins |
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| | Humans |
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| | Male |
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| | microRNA |
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| | MicroRNAs |
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| | Middle Aged |
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| | patient survival |
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| | Promoter Regions, Genetic |
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| | Signal Transduction |
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| | Tissue Array Analysis |
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| | Tumor Suppressor Proteins |
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| | Ubiquitin-Protein Ligases |
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| K10plus-PPN: | 1702052435 |
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| Verknüpfungen: | → Zeitschrift |
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Cadherin-6 is a putative tumor suppressor and target of epigenetically dysregulated miR-429 in cholangiocarcinoma / Goeppert, Benjamin [VerfasserIn]; 18 August 2016 (Online-Ressource)
