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...

Verfasser: Dhayat, Sameer
Mardin, Wolf Arif Mithat
Seggewiß, Jochen
Ströse, Anda Jana
Matuszcak, Christiane
Hummel, Richard
Senninger, Norbert
Mees, Sören Torge
Haier, Jörg
FB/Einrichtung:FB 05: Medizinische Fakultät
Dokumenttypen:Artikel
Medientypen:Text
Erscheinungsdatum:2015
Publikation in MIAMI:14.04.2016
Datum der letzten Änderung:31.07.2020
Angaben zur Ausgabe:[Electronic ed.]
Quelle:PLoS ONE 10 (2015) 11, e0143755, 1-21
Fachgebiet (DDC):610: Medizin und Gesundheit
Lizenz:CC BY 4.0
Sprache:English
Anmerkungen:Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF-Dokument
ISSN:1932-6203
URN:urn:nbn:de:hbz:6-76229530002
Weitere Identifikatoren:DOI: 10.1371/journal.pone.0143755
Permalink:https://nbn-resolving.de/urn:nbn:de:hbz:6-76229530002
Onlinezugriff: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