Latest Publications

@article{slabakova_alternative_2017,

title = {Alternative mechanisms of miR-34a regulation in cancer.},

author = {Eva Slabáková and Zoran Culig and Ján Remšík and Karel Souček},

doi = {10.1038/cddis.2017.495},

issn = {2041-4889},

year  = {2017},

date = {2017-10-01},

journal = {Cell death & disease},

volume = {8},

number = {10},

pages = {e3100},

abstract = {MicroRNA miR-34a is recognized as a master regulator of tumor suppression. The strategy of miR-34a replacement has been investigated in clinical trials as the first attempt of miRNA application in cancer treatment. However, emerging outcomes promote the re-evaluation of existing knowledge and urge the need for better understanding the complex biological role of miR-34a. The targets of miR-34a encompass numerous regulators of cancer cell proliferation, survival and resistance to therapy. MiR-34a expression is transcriptionally controlled by p53, a crucial tumor suppressor pathway, often disrupted in cancer. Moreover, miR-34a abundance is fine-tuned by context-dependent feedback loops. The function and effects of exogenously delivered or re-expressed miR-34a on the background of defective p53 therefore remain prominent issues in miR-34a based therapy. In this work, we review p53-independent mechanisms regulating the expression of miR-34a. Aside from molecules directly interacting with MIR34A promoter, processes affecting epigenetic regulation and miRNA maturation are discussed. Multiple mechanisms operate in the context of cancer-associated phenomena, such as aberrant oncogene signaling, EMT or inflammation. Since p53-dependent tumor-suppressive mechanisms are disturbed in a substantial proportion of malignancies, we summarize the effects of miR-34a modulation in cell and animal models in the clinically relevant context of disrupted or insufficient p53 function.},

note = {Place: England},

keywords = {*Genes, Animals, Epigenesis, Epithelial-Mesenchymal Transition/genetics, Gene Expression Regulation, Genetic/genetics, Humans, MicroRNAs/*genetics, Neoplasms/*genetics/*pathology, Neoplastic/genetics, Promoter Regions, Tumor Suppressor, Tumor Suppressor Protein p53/*genetics},

pubstate = {published},

tppubtype = {article}

}

@article{uhlirova_suv39h-_2010,

title = {SUV39h- and A-type lamin-dependent telomere nuclear rearrangement.},

author = {Radka Uhlírová and Andrea Harnicarová Horáková and Gabriela Galiová and Sona Legartová and Pavel Matula and Miloslava Fojtová and Miroslav Varecha and Jana Amrichová and Jan Vondrácek and Stanislav Kozubek and Eva Bártová},

doi = {10.1002/jcb.22466},

issn = {1097-4644 0730-2312},

year  = {2010},

date = {2010-04-01},

journal = {Journal of cellular biochemistry},

volume = {109},

number = {5},

pages = {915–926},

abstract = {Telomeres are specialized chromatin structures that are situated at the end of linear chromosomes and play an important role in cell senescence and immortalization. Here, we investigated whether changes in histone signature influence the nuclear arrangement and positioning of telomeres. Analysis of mouse embryonic fibroblasts revealed that telomeres were organized into specific clusters that partially associated with centromeric clusters. This nuclear arrangement was influenced by deficiency of the histone methyltransferase SUV39h, LMNA deficiency, and the histone deacetylase inhibitor Trichostatin A (TSA). Similarly, nuclear radial distributions of telomeric clusters were preferentially influenced by TSA, which caused relocation of telomeres closer to the nuclear center. Telomeres also co-localized with promyelocytic leukemia bodies (PML). This association was increased by SUV39h deficiency and decreased by LMNA deficiency. These differences could be explained by differing levels of the telomerase subunit, TERT, in SUV39h- and LMNA-deficient fibroblasts. Taken together, our data show that SUV39h and A-type lamins likely play a key role in telomere maintenance and telomere nuclear architecture.},

note = {Place: United States},

keywords = {*Gene Rearrangement, Animals, DNA-Binding Proteins/metabolism, Epigenesis, Fibroblasts/metabolism, Flow Cytometry, Genetic, Humans, Intranuclear Inclusion Bodies/metabolism, Lamin Type A/*metabolism, Methyltransferases/*metabolism, Mice, Protein Transport, rap1 GTP-Binding Proteins/metabolism, Repressor Proteins/*metabolism, Shelterin Complex, Telomerase/metabolism, Telomere-Binding Proteins, Telomere/genetics/*metabolism, Telomeric Repeat Binding Protein 1/metabolism},

pubstate = {published},

tppubtype = {article}

}

@article{pliskova_deregulation_2005,

title = {Deregulation of cell proliferation by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells reflects both genotoxic and nongenotoxic events.},

author = {Martina Plísková and Jan Vondrácek and Borivoj Vojtesek and Alois Kozubík and Miroslav Machala},

doi = {10.1093/toxsci/kfi040},

issn = {1096-6080 1096-0929},

year  = {2005},

date = {2005-02-01},

journal = {Toxicological sciences : an official journal of the Society of Toxicology},

volume = {83},

number = {2},

pages = {246–256},

abstract = {Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are carcinogens suggested to be involved in development of human cancer. Several recent studies have reported that PAHs can activate estrogen receptors (ER), either directly or indirectly by producing estrogenic metabolites. We hypothesized that the activation of ER by PAHs or their metabolites could induce cell proliferation in estrogen-sensitive cells. In the present study, we found that two PAHs, benz[a]anthracene (BaA) and BaP, can stimulate proliferation of human breast carcinoma MCF-7 cells at concentrations 100 nM and higher. This effect was ER-dependent, because it was blocked by the pure antiestrogen ICI 182,780. Although both PAHs partially inhibited S-phase entry and DNA synthesis induced by 17beta-estradiol, they stimulated S-phase entry when applied to MCF-7 cells synchronized by serum deprivation. This was in contrast with model antiestrogenic aryl hydrocarbon receptor ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, which fully suppressed S-phase entry. BaP, which is a strong mutagen, was found to induce p53 tumor suppressor expression, a partial S-phase arrest and at higher concentrations also cell death. Pifithrin-alpha, a synthetic inhibitor of p53 activity, abolished both S-phase arrest and apoptosis induced by genotoxic PAHs, and it potentiated the proliferative effect of BaP. Thus, both genotoxic and nongenotoxic events seem to interact in the effects of BaP on cell proliferation. Taken together, our data indicate that both BaA and BaP can stimulate cell proliferation through activation of ER. The proliferative effects of these carcinogenic compounds might contribute to tumor promotion in estrogen-sensitive tissues.},

note = {Place: United States},

keywords = {Benz(a)Anthracenes/*toxicity, Benzo(a)pyrene/*toxicity, Benzothiazoles, Breast Neoplasms/drug therapy/*genetics/metabolism, Bromodeoxyuridine/metabolism, Carcinogens/*toxicity, Carcinoma/drug therapy/*genetics/metabolism, Cell Cycle/drug effects, Cell Line, Cell Proliferation/*drug effects, Cell Survival/drug effects, DNA Replication/drug effects, Dose-Response Relationship, Drug, Drug Interactions, Epigenesis, Estradiol/*analogs & derivatives/pharmacology, Estrogen, Estrogen Antagonists/pharmacology, Female, Fulvestrant, Genetic, Humans, Receptors, Thiazoles/pharmacology, Toluene/*analogs & derivatives/pharmacology, Tumor, Tumor Suppressor Protein p53/antagonists & inhibitors/genetics/metabolism},

pubstate = {published},

tppubtype = {article}

}