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

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 expressio...

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Bibliographic Details
Published in:PloS one 2015-11, Vol.10 (11), p.e0143755
Main Authors: Dhayat, Sameer A, Mardin, Wolf Arif, Seggewiß, Jochen, Ströse, Anda Jana, Matuszcak, Christiane, Hummel, Richard, Senninger, Norbert, Mees, Sören Torge, Haier, Jörg
Format: Article
Language:English
Subjects:
Adenocarcinoma
Antimetabolites, Antineoplastic - pharmacology
Apoptosis
Bcl-2 protein
Cancer therapies
Carcinoma
Carcinoma, Pancreatic Ductal - drug therapy
Carcinoma, Pancreatic Ductal - genetics
Carcinoma, Pancreatic Ductal - metabolism
Care and treatment
Cell culture
Cell cycle
Cell death
Cell Line, Tumor
Cell survival
Chemoresistance
Chemotherapy
Cloning
Cluster Analysis
Computational Biology - methods
Cytotoxicity
Deoxycytidine - analogs & derivatives
Deoxycytidine - pharmacology
DNA microarrays
Dosage and administration
Drug Resistance, Neoplasm - genetics
Gemcitabine
Gene expression
Gene Expression Profiling
Genes, p53
Humans
Insulin-like growth factors
Kinases
Material requirements planning
Medical prognosis
Medical research
MicroRNA
MicroRNAs
MicroRNAs - genetics
miRNA
MRP1 protein
Mutation
p53 Protein
Pancreas
Pancreatic cancer
Pancreatic Neoplasms
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Phenols
Proteins
Regulators
Reproducibility of Results
Ribonucleic acid
Risk factors
RNA
RNA Interference
RNA, Messenger - genetics
Surgery
Toxicity
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Summary: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. 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. Both established PDAC clones showed a significant resistance to gemcitabine (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0143755