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Extracellular microRNAs in hematological malignancies and their use for diagnosis and treatment monitoring
Šulcová, Dominika ; Pospíšil, Vít (advisor) ; Čermák, Vladimír (referee)
MicroRNAs are short non-coding RNAs that negatively regulate gene expression at post-transcriptional level by interfering with mRNA translation and stability. Recently, microRNAs were surprisingly found to be present in various body fluids including blood plasma and serum, cerebrospinal fluid, saliva, milk or urine. These extracellular microRNAs are resistant to RNases and stable in high temperature or pH. Extreme stability of extracellular microRNAs is caused by their association with protective protein complexes (mostly with Argonaute proteins). MicroRNAs are frequently deregulated in cancer and specific tumor- related microRNAs can be also detected in body fluids, indicating that extracellular microRNAs can be used as tumor specific markers. This Bachelor thesis reviews basic principles of microRNA function and biogenesis with focus on extracellular microRNAs and their role in intercellular communication, and it highlights the role of extracellular microRNAs in hematological malignancies and their possible use in diagnosis and treatment.
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Gut microbiota effect on neuropsychiatric diseases
Pospíšil, Vít ; Kostovčíková, Klára (advisor) ; Červená, Kateřina (referee)
The intestinal microbiome is formed by trillions of microorganisms that accompany us throughout our lives. Commensal gut microorganisms, as a complex system, interfere with diet processing and subsequent spectrum of released metabolites, which are involved in communication with other systems of the human body. Recently, a link between intestinal microbiota dysbiosis and activation of the immune response has begun to emerge. This pathophysiological condition is associated with the loosening of the tight junctions of the gut epithelial barrier, which could together with prolonged immune inflammation lead to what is known as irritable bowel syndrome. This disease is not only related to symptoms associated with bowel discomfort, but also to effects on afferent nerve endings. This connection has been called as the gut-brain axis and became the link between the gut microbiota and psychiatric diseases. This work is summing up the actual knowledge on this topic and offers a comprehensive overview of the subject from both an immunological and a microbiological point of view. Key words: gut-brain axis, depression, anxiety, antibiotics, antidepressants, probiotics, IBS
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Role of the oncogenic microRNAs miR-17-92 and miR-155 in the regulation of hematopoietic differentiation and leukemogenesis
Pospíšil, Vít ; Stopka, Tomáš (advisor) ; Pospíšek, Martin (referee) ; Machová Poláková, Kateřina (referee)
(English version): Hematopoietic differentiation is highly ordered multistep process, where generation of terminal blood cells is dependent upon coordinated regulation of gene expression by key regulators: transcription factors and mikroRNAs. PU.1 (Sfpi1) is a versatile hematopoetic transcription factor required for the proper generation of both myeloid and lymphoid lineages. MikroRNAs represent a novel class of ~22 nucleotide long non-coding posttranscriptional regulators that inhibit expression of genes by blocking protein translation or by mRNA degradation. In this PhD thesis I present research data documenting novel mechanisms of regulation and function of two oncogenic mikroRNAs, miR-17-92 cluster and miR-155 and myeloid transcriptional factors PU.1 upon macrophage differentiation of myeloid progenitors. The miR-17-92 cluster (Oncomir1) encodes seven related mikroRNAs that regulate cell proliferation, apoptosis and development and is overexpressed in number of malignancies including myeloid leukemia. Presented PhD thesis documents novel macrophage specific regulatory mechanisms involving the oncogenic cluster miR-17-92. Using transgenic PU.1-/- myeloid progenitors we show that upon macrophage differentiation, the transcription factor PU.1 induces the secondary determinant, the transcription...
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Model for study of transcription regulation of granulocytic genes MPO and MMP9 by different levels of PU.1 transcription factor
Chramostová, Kamila ; Pospíšil, Vít (advisor) ; Kleibl, Zdeněk (referee)
9 Abstract Enhancers are distal cis - regulatory DNA sequences that regulate (enhance) transcription of the respective gene driven by its promoter. Enhancers are found in non-coding DNA upstream or downstream of the gene coding sequence, or in introns or coding regions that are located up to hundreds kb away from the gene. Superenhancers are newly discovered clusters of multiple enhancers that play a vital role in activating tissue-specific genes, determining cell identity and regulating differentiation. PU.1 is the transcription factor (TF) that is necessary for normal haematopoiesis, specifically for the development of myeloid and lymphoid blood lineages. Distinct levels of PU.1 induce differentiation of hematopoietic cells into different cell lineages whereby disruption of PU.1 levels leads to leukemogenesis. High PU.1 levels stimulate macrophage development, while intermediate levels stimulate the development of granulocytes. This diploma thesis seeks to contribute to addressing the interesting biological question of what are the regulatory mechanisms to ensure that granulocytic genes are activated only at the intermediate concentration of PU.1, whereas macrophage genes are activated only at its high levels. The aim of this diploma thesis was to create a series of reporter vectors carrying regulatory...
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Extracellular microRNAs in hematological malignancies and their use for diagnosis and treatment monitoring
Šulcová, Dominika ; Pospíšil, Vít (advisor) ; Čermák, Vladimír (referee)
MicroRNAs are short non-coding RNAs that negatively regulate gene expression at post-transcriptional level by interfering with mRNA translation and stability. Recently, microRNAs were surprisingly found to be present in various body fluids including blood plasma and serum, cerebrospinal fluid, saliva, milk or urine. These extracellular microRNAs are resistant to RNases and stable in high temperature or pH. Extreme stability of extracellular microRNAs is caused by their association with protective protein complexes (mostly with Argonaute proteins). MicroRNAs are frequently deregulated in cancer and specific tumor- related microRNAs can be also detected in body fluids, indicating that extracellular microRNAs can be used as tumor specific markers. This Bachelor thesis reviews basic principles of microRNA function and biogenesis with focus on extracellular microRNAs and their role in intercellular communication, and it highlights the role of extracellular microRNAs in hematological malignancies and their possible use in diagnosis and treatment.
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Role of the oncogenic microRNAs miR-17-92 and miR-155 in the regulation of hematopoietic differentiation and leukemogenesis
Pospíšil, Vít ; Stopka, Tomáš (advisor) ; Pospíšek, Martin (referee) ; Machová Poláková, Kateřina (referee)
(English version): Hematopoietic differentiation is highly ordered multistep process, where generation of terminal blood cells is dependent upon coordinated regulation of gene expression by key regulators: transcription factors and mikroRNAs. PU.1 (Sfpi1) is a versatile hematopoetic transcription factor required for the proper generation of both myeloid and lymphoid lineages. MikroRNAs represent a novel class of ~22 nucleotide long non-coding posttranscriptional regulators that inhibit expression of genes by blocking protein translation or by mRNA degradation. In this PhD thesis I present research data documenting novel mechanisms of regulation and function of two oncogenic mikroRNAs, miR-17-92 cluster and miR-155 and myeloid transcriptional factors PU.1 upon macrophage differentiation of myeloid progenitors. The miR-17-92 cluster (Oncomir1) encodes seven related mikroRNAs that regulate cell proliferation, apoptosis and development and is overexpressed in number of malignancies including myeloid leukemia. Presented PhD thesis documents novel macrophage specific regulatory mechanisms involving the oncogenic cluster miR-17-92. Using transgenic PU.1-/- myeloid progenitors we show that upon macrophage differentiation, the transcription factor PU.1 induces the secondary determinant, the transcription...
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