RODRIGO, Miguel Angel Merlos, Hana BUCHTELOVA, Ana Maria Jimenez JIMENEZ, Pavlina ADAM, Petr BABULA, Zbynek HEGER and Vojtech ADAM. Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells. Cells. Basel: MDPI, 2019, vol. 8, No 3, p. 1-19. ISSN 2073-4409. Available from: https://dx.doi.org/10.3390/cells8030235.
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Basic information
Original name Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells
Authors RODRIGO, Miguel Angel Merlos (203 Czech Republic), Hana BUCHTELOVA (203 Czech Republic), Ana Maria Jimenez JIMENEZ (203 Czech Republic), Pavlina ADAM (203 Czech Republic), Petr BABULA (203 Czech Republic, belonging to the institution), Zbynek HEGER (203 Czech Republic) and Vojtech ADAM (203 Czech Republic, guarantor).
Edition Cells, Basel, MDPI, 2019, 2073-4409.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10601 Cell biology
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 4.366
RIV identification code RIV/00216224:14110/19:00112796
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.3390/cells8030235
UT WoS 000465640400003
Keywords in English neuroblastoma; cisplatin; chemoresistance; microarray; lysosomes; transport
Tags 14110515, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 28/1/2020 12:35.
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.
Links
LQ1601, research and development projectName: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR
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