Journal Article

DKFZ-2017-01672

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression.

Botla, S. K. (First author)DKFZ* ; Savant, S.DKFZ* ; Jandaghi, P.DKFZ* ; Bauer, A.DKFZ* ; Mücke, O.DKFZ* ; Moskalev, E. A. ; Neoptolemos, J. P. ; Costello, E. ; Greenhalf, W. ; Scarpa, A. ; Gaida, M. M. ; Büchler, M. W. ; Strobel, O. ; Hackert, T. ; Giese, N. A. ; Augustin, H.DKFZ* ; Hoheisel, J. (Last author)DKFZ*

2016
AACR Philadelphia, Pa.

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/0008-5472.CAN-15-0390

Abstract: 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.

Keyword(s): Cadherins ; MIRN192 microRNA, human ; MicroRNAs ; Plasminogen Activator Inhibitor 1 ; SERPINE1 protein, human ; Vimentin

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Contributing Institute(s):

1. Funktionelle Genomanalyse (B070)
2. Vaskuläre Onkologie und Metastasierung (A190)
3. Epigenomik und Krebsrisikofaktoren (C010)
4. DKTK Heidelberg (L101)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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