Analýza exprese microRNA u vybraných hematologických malignit

Bc. Marek Mráz, Ph.D.

Master's thesis

Analysis of expression of microRNA in selected haematologic malignants

Abstract:

MicroRNAs (miRNAs) are short 20–22 nucleotide RNA molecules that function as negative regulators of gene expression in eukaryotic organisms. RNA mediated gene silencing pathways have essential roles in development, cell differentiation, cell proliferation, cell death, chromosome structure and virus resistance. These highly conserved RNAs regulating gene expression constitute about 3-5% of predicted genes in animals genomes, and 20-30% of protein-coding genes are probably regulated by miRNAs. MiRNAs are associated with RNA-induced silencing complex (RISC), which was identified before to repress the translation of mRNA by RNA interference (RNAi) mechanism. MiRNAs associate with RISC and bind to target mRNAs through partly complementary sequences and repress their translation. It results in the decresed level of the protein encoded by the mRNA. A single miRNA can bind multiple genes (based on incomplete complementarity) and have a possible profound effect on cell physiology. Moreover, many studies have shown that miRNAs are aberrantly expressed in cancer cells, suggesting that they might act as a novel class of oncogenes or tumor suppressors. A possibility to use microRNA signatures for a specific cancer classification has also been demonstrated. The field of microRNAs is not fully understood and their research is continuously in a dynamic progress. In this work I have analyzed miRNAs expression in B-chronic lymphocytic leukemia (CLL). The aim of this study was to identify miRNAs, which could have a potential role in CLL pathogenesis and might be useful as prognostic markers. Author primarily focused on the identification of microRNAs abnormally expressed in a CLL subtype with poor prognosis harboring a deletion and/or mutation of the TP53 (p53 gene). The analysis of microRNAs expression in these samples was not yet published and our primary results show that microRNAs may play a role in the pathogenesis of this chronic lymphocytic leukemia subtype.

Keywords

CLL, miRNA, microRNA, RNAi, p53, miR-34, chronická lymfatická leukémie, nádory, leukémie, lymfom, lymphomy, RNA interference, siRNA, shRNA

Language used: Czech

Date on which the thesis was submitted / produced: 15. 5. 2008

Thesis defence

• Date of defence: 16. 6. 2008
• Supervisor: prof. RNDr. Šárka Pospíšilová, Ph.D.

Masaryk University

Faculty of Science

Master programme / field:
Biology / Molecular Biology and Genetics