%0 Journal Article
%A Botla, Sandeep K
%A Savant, Soniya
%A Jandaghi, Pouria
%A Bauer, Andrea
%A Mücke, Oliver
%A Moskalev, Evgeny A
%A Neoptolemos, John P
%A Costello, Eithne
%A Greenhalf, William
%A Scarpa, Aldo
%A Gaida, Matthias M
%A Büchler, Markus W
%A Strobel, Oliver
%A Hackert, Thilo
%A Giese, Nathalia A
%A Augustin, Hellmut
%A Hoheisel, Jörg
%T Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression.
%J Cancer research
%V 76
%N 14
%@ 1538-7445
%C Philadelphia, Pa.
%I AACR
%M DKFZ-2017-01672
%P 4149 - 4159
%D 2016
%X Pancreatic ductal adenocarcinoma (PDAC) is characterized by very early metastasis, suggesting the hypothesis that metastasis-associated changes may occur prior to actual tumor formation. In this study, we identified miR-192 as an epigenetically regulated suppressor gene with predictive value in this disease. miR-192 was downregulated by promoter methylation in both PDAC and chronic pancreatitis, the latter of which is a major risk factor for the development of PDAC. Functional studies in vitro and in vivo in mouse models of PDAC showed that overexpression of miR-192 was sufficient to reduce cell proliferation and invasion. Mechanistic analyses correlated changes in miR-192 promoter methylation and expression with epithelial-mesenchymal transition. Cell proliferation and invasion were linked to altered expression of the miR-192 target gene SERPINE1 that is encoding the protein plasminogen activator inhibitor-1 (PAI-1), an established regulator of these properties in PDAC cells. Notably, our data suggested that invasive capacity was altered even before neoplastic transformation occurred, as triggered by miR-192 downregulation. Overall, our results highlighted a role for miR-192 in explaining the early metastatic behavior of PDAC and suggested its relevance as a target to develop for early diagnostics and therapy. Cancer Res; 76(14); 4149-59. ©2016 AACR.
%K Cadherins (NLM Chemicals)
%K MIRN192 microRNA, human (NLM Chemicals)
%K MicroRNAs (NLM Chemicals)
%K Plasminogen Activator Inhibitor 1 (NLM Chemicals)
%K SERPINE1 protein, human (NLM Chemicals)
%K Vimentin (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:27216198
%R 10.1158/0008-5472.CAN-15-0390
%U https://inrepo02.dkfz.de/record/125546