MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma

Background: No reliable predictors of susceptibility to gemcitabine chemotherapy exist in pancreatic ductal adenocarcinoma (PDAC). MicroRNAs (miR) are epigenetic gene regulators with tumorsuppressive or oncogenic roles in various carcinomas. This study assesses chemoresistant PDAC for its specific m...

Authors: Dhayat, Sameer A.
Mardin, Wolf Arif Mithat
Seggewiß, Jochen
Ströse, Anda Jana
Matuszcak, Christiane
Hummel, Richard
Senninger, Norbert
Mees, Sören Torge
Haier, Jörg
Division/Institute:FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2015
Date of publication on miami:14.04.2016
Modification date:11.07.2019
Edition statement:[Electronic ed.]
Source:PLoS ONE 10 (2015) 11, e0143755, 1-21
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Notes:Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
ISSN:1932-6203
URN:urn:nbn:de:hbz:6-76229530002
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-76229530002
Other Identifiers:DOI: 10.1371/journal.pone.0143755
Digital documents:journal.pone.0143755.PDF

Background: No reliable predictors of susceptibility to gemcitabine chemotherapy exist in pancreatic ductal adenocarcinoma (PDAC). MicroRNAs (miR) are epigenetic gene regulators with tumorsuppressive or oncogenic roles in various carcinomas. This study assesses chemoresistant PDAC for its specific miR expression pattern. Methods: Gemcitabine-resistant variants of two mutant p53 human PDAC cell lines were established. Survival rates were analyzed by cytotoxicity and apoptosis assays. Expression of 1733 human miRs was investigated by microarray and validated by qRT-PCR. After in-silico analysis of specific target genes and proteins of dysregulated miRs, expression of MRP-1, Bcl-2, mutant p53, and CDK1 was quantified by Western blot. Results: Both established PDAC clones showed a significant resistance to gemcitabine (p