Publication detail

Transcriptomic landscape of cisplatin-resistant neuroblastoma cells

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

Original Title

Transcriptomic landscape of cisplatin-resistant neuroblastoma cells

Type

journal article in Web of Science

Language

English

Original Abstract

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.

Keywords

neuroblastoma; cisplatin; chemoresistance; microarray; lysosomes; transport

Authors

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

Released

31. 3. 2019

Publisher

MDPI

ISBN

2073-4409

Periodical

Cells

Year of study

8

Number

3

State

Swiss Confederation

Pages from

1

Pages to

19

Pages count

19

URL

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

Full text in the Digital Library

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"
}