Detail publikace

Transcriptomic landscape of cisplatin-resistant neuroblastoma cells

MERLOS RODRIGO, M. BUCHTELOVÁ, H. JIMENEZ JIMENEZ, A. ADAM, P. BABULA, P. HEGER, Z. ADAM, V.

Originální název

Transcriptomic landscape of cisplatin-resistant neuroblastoma cells

Typ

článek v časopise ve Web of Science, Jimp

Jazyk

angličtina

Originální abstrakt

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.

Klíčová slova

neuroblastoma; cisplatin; chemoresistance; microarray; lysosomes; transport

Autoři

MERLOS RODRIGO, M.; BUCHTELOVÁ, H.; JIMENEZ JIMENEZ, A.; ADAM, P.; BABULA, P.; HEGER, Z.; ADAM, V.

Vydáno

31. 3. 2019

Nakladatel

MDPI

ISSN

2073-4409

Periodikum

Cells

Ročník

8

Číslo

3

Stát

Švýcarská konfederace

Strany od

1

Strany do

19

Strany počet

19

URL

http://www.mdpi.com/2073-4409/8/3/235

Plný text v Digitální knihovně

http://hdl.handle.net/11012/180502

BibTex

@article{BUT156829,
  author="Miguel Ángel {Merlos Rodrigo} and Hana {Michálková} and Ana Maria {Jimenez Jimenez} and Pavlína {Adam} and Petr {Babula} and Zbyněk {Heger} and Vojtěch {Adam}",
  title="Transcriptomic landscape of cisplatin-resistant neuroblastoma cells",
  journal="Cells",
  year="2019",
  volume="8",
  number="3",
  pages="1--19",
  doi="10.3390/cells8030235",
  issn="2073-4409",
  url="http://www.mdpi.com/2073-4409/8/3/235"
}