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Identification of genes responsible for tumor induction with avian retroviruses subgroup J
Gašpareková, Mária ; Pečenka, Vladimír (advisor) ; Španielová, Hana (referee)
Retroviruses are viruses which are able to integrate to genome of host cell. Nonrandom integration of provirus near or inside some cellular genes may result in their deregulation, activation or silencing. This can later lead to cell transformation and tumor formation. This thesis discusses identification of viral integration sites (VIS) and common integration sites (CIS) in tumors originating from different organs (mostly kidneys, lungs and liver) with using mostly avian retroviruses subgroup J, specifically first natural isolate HPRS-103 and laboratory made virus MAV-J, which was made by replacing gene envB by envJ. Infection was made in ovo using chicken breeds Brown Leghorn and White Leghorn and tumors were isolated from 8 to 28 weeks after infection. For molecular analyses was used inverse PCR method and sequencing. From 74 molecularly analyzed tumors there was detected 373 VIS and 6 CIS with statistical significance over 2.10-2 . Gene with the highest number of hits was FRK (14 times), then TERT (5 times), CTDSPL (5 times), EGFR/ERBB1 (3 times), MYB (3 times) and MYC (3 times). Except 6 CIS there were other genes found, which had smaller statistical significance. Keywords: retrovirus, insertional mutagenesis, subgroup J, oncogenesis, oncogenes, MAV-J, HPRS-103, proviral integration sites, tumors
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Raccoon polyomavirus: example or exception of polyomavirus driven oncogenesis?
Schreiberová, Lucie ; Španielová, Hana (advisor) ; Hirsch, Ivan (referee)
Polyomaviruses (PyV) are widespread through human and animal populations and typically associated with asymptomatic persistent infection. Rarely, natural PyV infections can lead to oncogenic transformation. Virus genome is usually integrated into the host DNA of tumour tissue. Over the past few years, an increased number of very aggressive brain tumours and olfactory tumours have been observed in raccoons. These tumours are associated with the newly discovered raccoon polyomavirus, which was found as an intact episome in host cells. This bachelor thesis is therefore focused on comparison of current state of knowledge on raccoon polyomavirus with previously described mechanisms of PyV tumorogenesis. Unlike for other PyVs, the fact that primary neuronal stem cell infection is most likely to occur can play a key role in raccoon polyomavirus driven oncogenesis. Tumours also exhibit unusually high expression of virus-encoded micro RNA that can be connected with tumour induction. Similary to other tumours caused by PyV, a large amount of early viral proteins with oncogenic potential is found in tumours. Revealing unknown factors responsible for the development of tumours caused by raccoon polyomavirus may help in understanding of mechanisms of oncogenesis. Key words Polyomavirus, oncogenesis, raccoon...
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MicroRNAs in Human Cancers Associated with Viral Infections
Dvořáková, Lucie ; Tachezy, Ruth (advisor) ; Drda Morávková, Alena (referee)
MicroRNA (miRNA) are short single-stranded RNAs that do not encode proteins. Their main function is the regulation of the gene expression on the level of translation. This regulation is mediated by the binding of miRNA to the partially complementary segments of mRNA, both cellular or viral. It is estimated that miRNAs affect expression of at least one third of human genes and thereby influence regulation of cellular growth, differentation and apoptosis of cells. Recently the miRNAs encoded mainly by DNA viruses were discovered. These miRNAs enhance the persistence of viral infection in the host and can contribute to malignant transformation. However, the oncogenesis is also significantly affected by the regulation of cellular miRNAs expression by viral proteins. The miRNA research is topical. MiRNAs are considered as potential biomarkers and their utilization as a cancer therapy is being intensely explored. In this thesis, I'm describing the biogenesis and regulatory functions of miRNAs. I'm also presenting an overview of viral miRNAs focusing on human oncogenic viruses which do not only code their own miRNAs but also influence the expression of the host miRNAs. Finally, I am focusing on current clinical applications of miRNA. Key words: viral miRNA, cellular miRNA, oncogenesis, viral infections,...
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