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

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MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma. / Dhayat, Sameer A; Mardin, Wolf Arif; Seggewiß, Jochen; Ströse, Anda Jana; Matuszcak, Christiane; Hummel, Richard; Senninger, Norbert; Mees, Sören Torge; Haier, Jörg.

in: PLOS ONE, Jahrgang 10, Nr. 11, 2015, S. e0143755.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Dhayat, SA, Mardin, WA, Seggewiß, J, Ströse, AJ, Matuszcak, C, Hummel, R, Senninger, N, Mees, ST & Haier, J 2015, 'MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma', PLOS ONE, Jg. 10, Nr. 11, S. e0143755. https://doi.org/10.1371/journal.pone.0143755

APA

Dhayat, S. A., Mardin, W. A., Seggewiß, J., Ströse, A. J., Matuszcak, C., Hummel, R., Senninger, N., Mees, S. T., & Haier, J. (2015). MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma. PLOS ONE, 10(11), e0143755. https://doi.org/10.1371/journal.pone.0143755

Vancouver

Dhayat SA, Mardin WA, Seggewiß J, Ströse AJ, Matuszcak C, Hummel R et al. MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma. PLOS ONE. 2015;10(11):e0143755. https://doi.org/10.1371/journal.pone.0143755

Bibtex

@article{deb73aa8c8ae4786a8c560b4ff4c0d2e,
title = "MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma",
abstract = "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<0.02) with low apoptosis rate (p<0.001) vs. parental cells. MiR-screening revealed significantly upregulated (miR-21, miR-99a, miR-100, miR-125b, miR-138, miR-210) and downregulated miRs (miR-31*, miR-330, miR-378) in chemoresistant PDAC (p<0.05). Bioinformatic analysis suggested involvement of these miRs in pathways controlling cell death and cycle. MRP-1 (p<0.02) and Bcl-2 (p<0.003) were significantly overexpressed in both resistant cell clones and mutant p53 (p = 0.023) in one clone.CONCLUSION: Consistent miR expression profiles, in part regulated by mutant TP53 gene, were identified in gemcitabine-resistant PDAC with significant MRP-1 and Bcl-2 overexpression. These results provide a basis for further elucidation of chemoresistance mechanisms and therapeutic approaches to overcome chemoresistance in PDAC.",
author = "Dhayat, {Sameer A} and Mardin, {Wolf Arif} and Jochen Seggewi{\ss} and Str{\"o}se, {Anda Jana} and Christiane Matuszcak and Richard Hummel and Norbert Senninger and Mees, {S{\"o}ren Torge} and J{\"o}rg Haier",
year = "2015",
doi = "10.1371/journal.pone.0143755",
language = "English",
volume = "10",
pages = "e0143755",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

RIS

TY - JOUR

T1 - MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma

AU - Dhayat, Sameer A

AU - Mardin, Wolf Arif

AU - Seggewiß, Jochen

AU - Ströse, Anda Jana

AU - Matuszcak, Christiane

AU - Hummel, Richard

AU - Senninger, Norbert

AU - Mees, Sören Torge

AU - Haier, Jörg

PY - 2015

Y1 - 2015

N2 - 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<0.02) with low apoptosis rate (p<0.001) vs. parental cells. MiR-screening revealed significantly upregulated (miR-21, miR-99a, miR-100, miR-125b, miR-138, miR-210) and downregulated miRs (miR-31*, miR-330, miR-378) in chemoresistant PDAC (p<0.05). Bioinformatic analysis suggested involvement of these miRs in pathways controlling cell death and cycle. MRP-1 (p<0.02) and Bcl-2 (p<0.003) were significantly overexpressed in both resistant cell clones and mutant p53 (p = 0.023) in one clone.CONCLUSION: Consistent miR expression profiles, in part regulated by mutant TP53 gene, were identified in gemcitabine-resistant PDAC with significant MRP-1 and Bcl-2 overexpression. These results provide a basis for further elucidation of chemoresistance mechanisms and therapeutic approaches to overcome chemoresistance in PDAC.

AB - 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<0.02) with low apoptosis rate (p<0.001) vs. parental cells. MiR-screening revealed significantly upregulated (miR-21, miR-99a, miR-100, miR-125b, miR-138, miR-210) and downregulated miRs (miR-31*, miR-330, miR-378) in chemoresistant PDAC (p<0.05). Bioinformatic analysis suggested involvement of these miRs in pathways controlling cell death and cycle. MRP-1 (p<0.02) and Bcl-2 (p<0.003) were significantly overexpressed in both resistant cell clones and mutant p53 (p = 0.023) in one clone.CONCLUSION: Consistent miR expression profiles, in part regulated by mutant TP53 gene, were identified in gemcitabine-resistant PDAC with significant MRP-1 and Bcl-2 overexpression. These results provide a basis for further elucidation of chemoresistance mechanisms and therapeutic approaches to overcome chemoresistance in PDAC.

U2 - 10.1371/journal.pone.0143755

DO - 10.1371/journal.pone.0143755

M3 - SCORING: Journal article

C2 - 26606261

VL - 10

SP - e0143755

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 11

ER -