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@article{1612438,
author = {Rodrigo, Miguel Angel Merlos and Buchtelova, Hana and Jimenez, Ana Maria Jimenez and Adam, Pavlina and Babula, Petr and Heger, Zbynek and Adam, Vojtech},
article_location = {Basel},
article_number = {3},
doi = {http://dx.doi.org/10.3390/cells8030235},
keywords = {neuroblastoma; cisplatin; chemoresistance; microarray; lysosomes; transport},
language = {eng},
issn = {2073-4409},
journal = {Cells},
title = {Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells},
url = {http://dx.doi.org/10.3390/cells8030235},
volume = {8},
year = {2019}
}
TY - JOUR
ID - 1612438
AU - Rodrigo, Miguel Angel Merlos - Buchtelova, Hana - Jimenez, Ana Maria Jimenez - Adam, Pavlina - Babula, Petr - Heger, Zbynek - Adam, Vojtech
PY - 2019
TI - Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells
JF - Cells
VL - 8
IS - 3
SP - 1-19
EP - 1-19
PB - MDPI
SN - 20734409
KW - neuroblastoma
KW - cisplatin
KW - chemoresistance
KW - microarray
KW - lysosomes
KW - transport
UR - http://dx.doi.org/10.3390/cells8030235
L2 - http://dx.doi.org/10.3390/cells8030235
N2 - The efficiency of cisplatin (CDDP) is significantly hindered by the development of resistance during the treatment course. To gain a detailed understanding of the molecular mechanisms underlying the development of cisplatin resistance, we comparatively analyzed established a CDDP-resistant neuroblastoma cell line (UKF-NB-4(CDDP)) and its susceptible parental cells (UKF-NB-4). We verified increased chemoresistance of UKF-NB-4(CDDP) cells by analyzing the viability, induction of apoptosis and clonal efficiency. To shed more light on this phenomenon, we employed custom cDNA microarray (containing 2234 probes) to perform parallel transcriptomic profiling of RNA and identified that 139 genes were significantly up-regulated due to CDDP chemoresistance. The analyses of molecular pathways indicated that the top up-regulation scoring functions were response to stress, abiotic stimulus, regulation of metabolic process, apoptotic processes, regulation of cell proliferation, DNA repair or regulation of catalytic activity, which was also evidenced by analysis of molecular functions revealing up-regulation of genes encoding several proteins with a wide-spectrum of enzymatic activities. Functional analysis using lysosomotropic agents chloroquine and bafilomycin A1 validated their potential to re-sensitize UKF-NB-4(CDDP) cells to CDDP. Taken together, the identification of alterations in specific genes and pathways that contribute to CDDP chemoresistance may potentially lead to a renewed interest in the development of novel rational therapeutics and prognostic biomarkers for the management of CDDP-resistant neuroblastoma.
ER -
RODRIGO, Miguel Angel Merlos, Hana BUCHTELOVA, Ana Maria Jimenez JIMENEZ, Pavlina ADAM, Petr BABULA, Zbynek HEGER a Vojtech ADAM. Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells. \textit{Cells}. Basel: MDPI, 2019, roč.~8, č.~3, s.~1-19. ISSN~2073-4409. Dostupné z: https://dx.doi.org/10.3390/cells8030235.
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