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The role of microRNAs in lymphomas with a focus on miR-155
Hušková, Hana ; Stopka, Tomáš (advisor) ; Svoboda, Petr (referee)
MicroRNAs (miRNAs) are 19-25 nucleotide noncoding RNAs which regulate the expression of target mRNAs at both posttranscriptional and translational level. The physiological functions of miRNAs include development, differentiation, cell cycle regulation and apoptosis. miRNA deregulation has been found in various human diseases, including lymphoproliferative disorders. This Bachelor thesis provides introduction to delineate roles of miRNAs in normal hematopoiesis and cites recent publications on miRNAs in lymphomas with a focus on the role of miR-155. Key words microRNA, hematopoiesis, lymphoma, miR-155
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Investigating critical mechanisms of oncogenesis using cell model systems
Hušková, Hana ; Stopka, Tomáš (advisor) ; Macůrek, Libor (referee) ; Vojtěšek, Bořivoj (referee)
(EN) Humans and cells in their bodies are exposed to various mutagens in their lifetime that cause DNA damage and mutations, which affect the biology and physiology of the target cell, and can lead to the expansion of an immortalized cell clone. Genome-wide massively parallel sequencing allows the identification of DNA mutations in the coding sequences (whole exome sequencing, WES), or even the entire genome of a tumour. Mutational signatures of individual mutagenic processes can be extracted from these data, as well as mutations in genes potentially important for cancer development ('cancer drivers', as opposed to 'passengers', which do not confer a comparative growth advantage to a cell clone). Many known mutational signatures do not yet have an attributed cause; and many known mutagens do not have an attributed signature. Similarly, it is estimated that many cancer driver genes remain to be identified. This Thesis proposes a system based on immortalization of mouse embryonic fibroblasts (MEF) upon mutagen treatment for modelling of mutational signatures and identification and testing of cancer driver genes and mutations. The signatures extracted from WES data of 25 immortalized MEF cell lines, which arose upon treatment with a variety of mutagens, showed that the assay recapitulates the...
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Up-regulation of microRNA miR-155 is reflected by low levels of its target mRNA encoding transcription factor PU.1 in primary tumors of human lymphomas
Hušková, Hana ; Stopka, Tomáš (advisor) ; Mráz, Marek (referee)
Lymphomas are heterogenous class of diseases characterized by proliferation of a malignant lymphocyte clone. MicroRNA miR-155 was found to be a key molecule in immune response, namely in inflammation and germinal reaction of B cells. On the other hand, miR-155 can drive lymphoproliferation in mouse and its levels were found to be elevated in certain lymphoma types in human. MiR-155 down-regulates expression of its target gene PU.1, a hematopoietic transcription factor important for B cell differentiation. Expression of the gene encoding miR-155, known as MIR155HG, is controled by several transcription factors, among them MYB, a member of an oncogenic E-box protein family. Levels of MYB itself are controled by microRNA miR-150. In this study, we measured levels of miR-155, PU.1, MYB and miR-150 in lymph nodes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL, N=20), diffuse large B-cell lymphoma (DLBCL, N=24), follicular lymphoma (FL, N=29), Hodgkin lymphoma (HL, N=25), marginal zone lymphoma (MZL, N=13), and mantle cell lymphoma (MCL, N=10). We also measured levels of these molecules in lymph nodes with the finding of strong inflammation (N=4). We found that patients of all the diagnoses except of MCL display heterogeneously elevated levels of miR-155 and correspondingly...
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The role of microRNAs in lymphomas with a focus on miR-155
Hušková, Hana ; Stopka, Tomáš (advisor) ; Svoboda, Petr (referee)
MicroRNAs (miRNAs) are 19-25 nucleotide noncoding RNAs which regulate the expression of target mRNAs at both posttranscriptional and translational level. The physiological functions of miRNAs include development, differentiation, cell cycle regulation and apoptosis. miRNA deregulation has been found in various human diseases, including lymphoproliferative disorders. This Bachelor thesis provides introduction to delineate roles of miRNAs in normal hematopoiesis and cites recent publications on miRNAs in lymphomas with a focus on the role of miR-155. Key words microRNA, hematopoiesis, lymphoma, miR-155
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Further education and personal development of employees at Prague City Hall
Syslová, Andrea ; Šikýř, Martin (advisor) ; Hušková, Hana (referee)
The thesis presents an analysis of the area of further education and personal development of local government employees, in particular of employees at Prague City Hall (MHMP). The focus is aimed primarily at mentoring project in MHMP, its principles and guidelines, there are listed the advantages and disadvantages of such a system and possible improvements. Based on identified weaknesses in the education strategy of MHMP the thesis suggests a training programme designed to improve the skills of leading managers in the areas of effective leadership and the staff motivation.
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