Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma
Cells

J 2019

Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells

RODRIGO, Miguel Angel Merlos, Hana BUCHTELOVA, Ana Maria Jimenez JIMENEZ, Pavlina ADAM, Petr BABULA et. al.

Základní údaje

Originální název

Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells

Autoři

RODRIGO, Miguel Angel Merlos (203 Česká republika), Hana BUCHTELOVA (203 Česká republika), Ana Maria Jimenez JIMENEZ (203 Česká republika), Pavlina ADAM (203 Česká republika), Petr BABULA (203 Česká republika, domácí), Zbynek HEGER (203 Česká republika) a Vojtech ADAM (203 Česká republika, garant)

Vydání

Cells, Basel, MDPI, 2019, 2073-4409

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.366

Kód RIV

RIV/00216224:14110/19:00112796

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.3390/cells8030235

UT WoS

000465640400003

Klíčová slova anglicky

neuroblastoma; cisplatin; chemoresistance; microarray; lysosomes; transport

Štítky

14110515, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 1. 2020 12:35, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

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. Cells. Basel: MDPI, 2019, roč. 8, č. 3, s. 1-19. ISSN 2073-4409. Dostupné z: https://dx.doi.org/10.3390/cells8030235.

@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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