2020
Nekvindova, Jana; Mrkvicova, Alena; Zubanova, Veronika; Vaculova, Alena Hyrslova; Anzenbacher, Pavel; Soucek, Pavel; Radova, Lenka; Slaby, Ondrej; Kiss, Igor; Vondracek, Jan; Spicakova, Alena; Bohovicova, Lucia; Fabian, Pavel; Kala, Zdenek; Palicka, Vladimir
Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450. Journal Article
In: Biochemical pharmacology, vol. 177, pp. 113912, 2020, ISSN: 1873-2968 0006-2952, (Place: England).
Abstract | Links | BibTeX | Tags: *Gene Expression Regulation, *Transcriptome, Adult, Aged, Carcinoma, Cohort Studies, CYP, Cytochrome P-450 Enzyme System/*genetics, Cytochrome P450, Cytoplasmic and Nuclear/genetics/metabolism, Drug metabolism, Enzymologic, Female, Gene Expression, Gene Expression Profiling, Hepatocellular carcinoma, Hepatocellular/*enzymology/pathology, Hepatocytes/metabolism, Humans, Inactivation, Liver Neoplasms/*enzymology/pathology, Liver/metabolism, Male, Metabolic/genetics, Middle Aged, Neoplasm Grading, Non-coding RNA, Receptors
@article{nekvindova_hepatocellular_2020,
title = {Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450.},
author = {Jana Nekvindova and Alena Mrkvicova and Veronika Zubanova and Alena Hyrslova Vaculova and Pavel Anzenbacher and Pavel Soucek and Lenka Radova and Ondrej Slaby and Igor Kiss and Jan Vondracek and Alena Spicakova and Lucia Bohovicova and Pavel Fabian and Zdenek Kala and Vladimir Palicka},
doi = {10.1016/j.bcp.2020.113912},
issn = {1873-2968 0006-2952},
year = {2020},
date = {2020-07-01},
journal = {Biochemical pharmacology},
volume = {177},
pages = {113912},
abstract = {Hepatocellular carcinoma (HCC) remains a highly prevalent and deadly disease, being among the top causes of cancer-related deaths worldwide. Despite the fact that the liver is the major site of biotransformation, studies on drug metabolizing enzymes in HCC are scarce. It is known that malignant transformation of hepatocytes leads to a significant alteration of their metabolic functions and overall deregulation of gene expression. Advanced stages of the disease are thus frequently associated with liver failure, and severe alteration of drug metabolism. However, the impact of dysregulation of metabolic enzymes on therapeutic efficacy and toxicity in HCC patients is largely unknown. Here we demonstrate a significant down-regulation in European Caucasian patients of cytochromes P450 (CYPs), the major xenobiotic-metabolizing enzymes, in HCC tumour samples as compared to their surrounding non-cancerous (reference) tissue. Moreover, we report for the first time the association of the unique CYP profiles with specific transcriptome changes, and interesting correlations with expression levels of nuclear receptors and with the histological grade of the tumours. Integrated analysis has suggested certain co-expression profiles of CYPs with lncRNAs that need to be further characterized. Patients with large tumours with down-regulated CYPs could be more vulnerable to drug toxicity; on the other hand, such tumours would eliminate drugs more slowly and should be more sensitive to pharmacotherapy (except in the case of pro-drugs where activation is necessary).},
note = {Place: England},
keywords = {*Gene Expression Regulation, *Transcriptome, Adult, Aged, Carcinoma, Cohort Studies, CYP, Cytochrome P-450 Enzyme System/*genetics, Cytochrome P450, Cytoplasmic and Nuclear/genetics/metabolism, Drug metabolism, Enzymologic, Female, Gene Expression, Gene Expression Profiling, Hepatocellular carcinoma, Hepatocellular/*enzymology/pathology, Hepatocytes/metabolism, Humans, Inactivation, Liver Neoplasms/*enzymology/pathology, Liver/metabolism, Male, Metabolic/genetics, Middle Aged, Neoplasm Grading, Non-coding RNA, Receptors},
pubstate = {published},
tppubtype = {article}
}
Hepatocellular carcinoma (HCC) remains a highly prevalent and deadly disease, being among the top causes of cancer-related deaths worldwide. Despite the fact that the liver is the major site of biotransformation, studies on drug metabolizing enzymes in HCC are scarce. It is known that malignant transformation of hepatocytes leads to a significant alteration of their metabolic functions and overall deregulation of gene expression. Advanced stages of the disease are thus frequently associated with liver failure, and severe alteration of drug metabolism. However, the impact of dysregulation of metabolic enzymes on therapeutic efficacy and toxicity in HCC patients is largely unknown. Here we demonstrate a significant down-regulation in European Caucasian patients of cytochromes P450 (CYPs), the major xenobiotic-metabolizing enzymes, in HCC tumour samples as compared to their surrounding non-cancerous (reference) tissue. Moreover, we report for the first time the association of the unique CYP profiles with specific transcriptome changes, and interesting correlations with expression levels of nuclear receptors and with the histological grade of the tumours. Integrated analysis has suggested certain co-expression profiles of CYPs with lncRNAs that need to be further characterized. Patients with large tumours with down-regulated CYPs could be more vulnerable to drug toxicity; on the other hand, such tumours would eliminate drugs more slowly and should be more sensitive to pharmacotherapy (except in the case of pro-drugs where activation is necessary).
2017
Boström, Johan; Sramkova, Zuzana; Salašová, Alena; Johard, Helena; Mahdessian, Diana; Fedr, Radek; Marks, Carolyn; Medalová, Jiřina; Souček, Karel; Lundberg, Emma; Linnarsson, Sten; Bryja, Vítězslav; Sekyrova, Petra; Altun, Mikael; Andäng, Michael
Comparative cell cycle transcriptomics reveals synchronization of developmental transcription factor networks in cancer cells. Journal Article
In: PloS one, vol. 12, no. 12, pp. e0188772, 2017, ISSN: 1932-6203, (Place: United States).
Abstract | Links | BibTeX | Tags: *Transcriptome, Algorithms, Cell Cycle Proteins/genetics/metabolism, Cell Cycle/*genetics, Cell Line, Humans, Neoplasms/genetics/*metabolism/pathology, Transcription Factors/*metabolism, Tumor
@article{bostrom_comparative_2017,
title = {Comparative cell cycle transcriptomics reveals synchronization of developmental transcription factor networks in cancer cells.},
author = {Johan Boström and Zuzana Sramkova and Alena Salašová and Helena Johard and Diana Mahdessian and Radek Fedr and Carolyn Marks and Jiřina Medalová and Karel Souček and Emma Lundberg and Sten Linnarsson and Vítězslav Bryja and Petra Sekyrova and Mikael Altun and Michael Andäng},
doi = {10.1371/journal.pone.0188772},
issn = {1932-6203},
year = {2017},
date = {2017-01-01},
journal = {PloS one},
volume = {12},
number = {12},
pages = {e0188772},
abstract = {The cell cycle coordinates core functions such as replication and cell division. However, cell-cycle-regulated transcription in the control of non-core functions, such as cell identity maintenance through specific transcription factors (TFs) and signalling pathways remains unclear. Here, we provide a resource consisting of mapped transcriptomes in unsynchronized HeLa and U2OS cancer cells sorted for cell cycle phase by Fucci reporter expression. We developed a novel algorithm for data analysis that enables efficient visualization and data comparisons and identified cell cycle synchronization of Notch signalling and TFs associated with development. Furthermore, the cell cycle synchronizes with the circadian clock, providing a possible link between developmental transcriptional networks and the cell cycle. In conclusion we find that cell cycle synchronized transcriptional patterns are temporally compartmentalized and more complex than previously anticipated, involving genes, which control cell identity and development.},
note = {Place: United States},
keywords = {*Transcriptome, Algorithms, Cell Cycle Proteins/genetics/metabolism, Cell Cycle/*genetics, Cell Line, Humans, Neoplasms/genetics/*metabolism/pathology, Transcription Factors/*metabolism, Tumor},
pubstate = {published},
tppubtype = {article}
}
The cell cycle coordinates core functions such as replication and cell division. However, cell-cycle-regulated transcription in the control of non-core functions, such as cell identity maintenance through specific transcription factors (TFs) and signalling pathways remains unclear. Here, we provide a resource consisting of mapped transcriptomes in unsynchronized HeLa and U2OS cancer cells sorted for cell cycle phase by Fucci reporter expression. We developed a novel algorithm for data analysis that enables efficient visualization and data comparisons and identified cell cycle synchronization of Notch signalling and TFs associated with development. Furthermore, the cell cycle synchronizes with the circadian clock, providing a possible link between developmental transcriptional networks and the cell cycle. In conclusion we find that cell cycle synchronized transcriptional patterns are temporally compartmentalized and more complex than previously anticipated, involving genes, which control cell identity and development.