Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

Journal article


Publication Details

Author(s): Botla SK, Savant S, Jandaghi P, Bauer AS, Muecke O, Moskalev E, Neoptolemos JP, Costello E, Greenhalf W, Scarpa A, Gaida MM, Buechler MW, Strobel O, Hackert T, Giese NA, Augustin HG, Hoheisel JD
Journal: Cancer Research
Publication year: 2016
Volume: 76
Journal issue: 14
Pages range: 4149-59
ISSN: 0008-5472


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.


FAU Authors / FAU Editors

Moskalev, Evgeny PD Dr.
Pathologisches Institut


External institutions with authors

Deutsches Krebsforschungszentrum (DKFZ)
The University of Liverpool
Universitätsklinikum Heidelberg
University of Verona / Università degli Studi di Verona


How to cite

APA:
Botla, S.K., Savant, S., Jandaghi, P., Bauer, A.S., Muecke, O., Moskalev, E.,... Hoheisel, J.D. (2016). Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression. Cancer Research, 76(14), 4149-59. https://dx.doi.org/10.1158/0008-5472.CAN-15-0390

MLA:
Botla, Sandeep K., et al. "Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression." Cancer Research 76.14 (2016): 4149-59.

BibTeX: 

Last updated on 2018-09-10 at 02:18