{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:25:12Z","timestamp":1778642712924,"version":"3.51.4"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T00:00:00Z","timestamp":1552348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","award":["CEITEC 2020 (LQ1601)"],"award-info":[{"award-number":["CEITEC 2020 (LQ1601)"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["759585"],"award-info":[{"award-number":["759585"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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-4CDDP) and its susceptible parental cells (UKF-NB-4). We verified increased chemoresistance of UKF-NB-4CDDP 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-4CDDP 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.<\/jats:p>","DOI":"10.3390\/cells8030235","type":"journal-article","created":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T04:07:37Z","timestamp":1552450057000},"page":"235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1920-0948","authenticated-orcid":false,"given":"Miguel Angel Merlos","family":"Rodrigo","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic"},{"name":"Central European Institute of Technology, Brno University of Technology, Technicka 3058\/10, CZ-616 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Buchtelova","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1736-492X","authenticated-orcid":false,"given":"Ana Maria Jimenez","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic"},{"name":"Central European Institute of Technology, Brno University of Technology, Technicka 3058\/10, CZ-616 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavlina","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Babula","sequence":"additional","affiliation":[{"name":"Central European Institute of Technology, Brno University of Technology, Technicka 3058\/10, CZ-616 00 Brno, Czech Republic"},{"name":"Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 753\/5, CZ-625 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3915-7270","authenticated-orcid":false,"given":"Zbynek","family":"Heger","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic"},{"name":"Central European Institute of Technology, Brno University of Technology, Technicka 3058\/10, CZ-616 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vojtech","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic"},{"name":"Central European Institute of Technology, Brno University of Technology, Technicka 3058\/10, CZ-616 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,12]]},"reference":[{"key":"ref_1","first-page":"1757","article-title":"Vandetanib inhibits cisplatin-resistant neuroblastoma tumor growth and invasion","volume":"39","author":"Li","year":"2018","journal-title":"Oncol. 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