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Background: Molecular pathogenesis of follicular lymphoma (FL) is characterized by substantial dysregulation of epigenetic regulators. Many cases of FL are associated with the aberrant expression of non-coding regulatory RNAs, namely microRNAs (miRNA). Here we studied changes in miRNA expression and their association with histological transformation of FL to diffuse large B-cell lymphoma (DLBCL)., Material and Methods: To identify changes in miRNA levels during FL transformation we performed a global expression analysis of 377 miRNAs in 16 samples (8 pairs) from FL patients vs. transformed FL (tFL) (TLDA miRNA cards; Thermo Fisher Scientific). The association of miRNA expression with clinical-biological characteristics and target proteins were further analyzed in a cohort of 89 FL patients., Results: The miRNA expression profiling of paired FL-tFL samples revealed statistically significant changes in the expression of five miRNAs (p < 0.05). Four of them were down-regulated and one was up-regulated in tFL compared to FL. Lower levels of one of these miRNA were also associated with higher proliferation rate of FL cells (Ki-67 > 20%), higher FLIPI score ( 3) and shorter overall survival of FL patients. Furthermore, we found that this miRNA regulates the levels of FOXP1 protein in FL. The patients with high-level FOXP1 expression (> 70% positive cells) had significantly shorter overall survival in comparison to those with low-level FOXP1 expression (< 30% positive cells). Moreover, FOXP1 protein levels were higher in most tFL samples compared to FL before transformation., Conclusion: We found miRNAs associated with the transformation of FL to a more aggressive DLBCL, and described that one of them could serve as a prognostic marker. We found that reduced expression of this tFL-associated miRNA results in increased levels of FOXP1 protein and we assume that the increased activity of FOXP1 proto-oncogene contributes to the histological transformation of FL.Key words: follicular lymphoma - microRNA - histological transformation This work was supported by Czech Ministry of Health registration No. 16-29622A. All rights reserved. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 5. 3. 2017Accepted: 26. 3. 2017.

Unlabelled: microRNAs (abbreviated miRNAs or miRs) represents one of the group of so called small non-coding RNAs which participate in the negative post-transcriptional regulation of gene expression. According to the base complementarity they target molecules of messenger RNAs (mRNAs) which results either in translational blockade or in degradation of target mRNA. One miRNA usually targets more mRNA and one mRNA is usually targeted by more than one miRNA - complicated and interconnected regulatory networks are thus created and their disruption leads to the abnormalities in development or results in the development of diseases. Within the past two decades, novel mechanisms were described that enable us to modulate miRNA levels (either causing upregulation or downregulation) - miRNAs can thus be considered as a novel potential group of therapeutic targets. First clinical trials using the blockade of liver specific miR-122 showed very promising results in the treatment of chronic hepatitis C virus infection. Results of preclinical and animal studies are also promising providing future rationale for the development of new therapeutics for various internal diseases including heart failure, bronchial asthma or inflammatory bowel diseases. Moreover, miRNAs are not only affecting the pathophysiology of internal diseases, but they can also reflect their presence - there is a group of miRNAs called extracellular, or circulating miRNAs, i.e. miRNAs that are present in extracellular space including all known body fluids such as plasma, serum, urine, saliva or sweat. Circulating miRNAs are stable; their levels are constant among the individuals of one species, methods determining their levels are reproducible and last but not least - levels of extracellular miRNAs differ between healthy and diseased individuals. They are released into the circulation either after the cell necrosis or by active transport. Except of being potential novel biomarkers, these miRNAs represent a novel mean of intercellular communication. Their levels thus reflect not only the organ damage but also the changes of the homeostasis during various illnesses. The aim of the current study is to provide the first insight into the miRNA world to clinicians, especially to internal medicine specialists. Using simple examples from clinical praxis or clinical pathophysiology, we are trying to present diagnostic and therapeutic potential that is hidden within these tiny interesting molecules., Key Words: circulating microRNA - diagnostics - internal diseases - microRNA - therapy.

Whole-genome sequencing analyses revealed that the majority of the human genome is transcribed and identified thousands of protein non-coding transcripts. Non-coding RNAs (ncRNAs) are divided into two main groups: small and long ncRNAs. This review is focused on the regulatory ncRNAs mainly on microRNAs and long ncRNAs. These ncRNAs regulate gene expression at the transcriptional and post-transcriptional levels. In this context, ncRNAs are involved in the regulation of most cellular processes and their deregulation has serious impacts on the phenotype. Hundreds of studies have implicated ncRNAs in the pathogenesis of many diseases ranging from metabolic disorders to diseases of organ systems as well as various types of cancers.Clinically, ncRNAs belong to a new generation of diagnostic and prognostic biomarkers with a great potential. Due to high tissue specificity and ability to regulate multiple genes often within one signaling pathway, ncRNAs represent attractive therapeutic targets. Increasing knowledge about a wide spectrum of ncRNA actions demonstrate a pivotal role of these transcripts in expression regulation. Many aspects of the ncRNA biology are still unclear and their understanding will provide us a new perspective on the complexity of the regulatory network.

Glioblastoma multiforme is the most common intracranial malignity of astrocyte origin in adults. Despite complex therapy consisting of maximal surgical resection, adjuvant concomitant chemoradiotherapy with temozolomide followed by temozolomide in monotherapy, the median of survival ranges between 12 and 15 months from dia-gnosis. This infaust prognosis is very often caused by both impossibility of achieving of sufficient radical surgical resection and tumor resistance to adjuvant therapy, which relates to the presence of glioblastoma stem cells. Similarly to normal stem cells, glioblastoma stem cells are capable of self -renewal, differentiation, and unlimited slow proliferation. Their resistance to conventional therapy is also due to higher expressions of DNA repair enzymes, antiapoptotic factors and multidrug transporters. Therefore, targeting these unique properties could be a novel promising therapeutic approach leading to more effective therapy and better prognosis of glioblastoma multiforme patients. One of the approaches how to successfully regulate above -mentioned properties is targeted regulation of microRNAs (miRNAs). These small noncoding RNA molecules posttranscriptionally regulate expression of more than 2/ 3 of all human genes that are also involved in stem cell associated signaling pathways. Moreover, deregulated expression of some miRNAs has been observed in many cancers, including glioblastoma multiforme.

MicroRNAs are an abundant class of noncoding RNAs (approx. 18- 25 nucleotides in length) that suppress translation through binding to their target mRNAs, eventually leading to mRNAs degradation. Sequences of these endogenous RNA molecules are highly conserved, even among unrelated species, indicating their involvement in basic bio-logical processes, such as development, differentiation, proliferation or apoptosis. MiRNAs also participate on regulation of cancer stem cell functioning, immune system and malignant transformation. This review provides a comprehensive overview of miRNAs functions in esophageal cancer, their roles in key pathogenetic pathways and disease development, as well as their potential usage in clinical routine as bio-markers improving dia-gnosis, prognosis and prediction of therapeutic response. Through regulation of signaling pathways important in malignant transformation, miRNAs present also promising therapeutic targets.

Neuroblastoma (NBL) is a typical childhood tumor developing from the precursor cells of the sympathetic nervous tissue and accounting for approximately 7% of total malignancies in pediatrics and 15% of deaths associated with this malignancy. MicroRNAs (miRNAs) are small single-stranded RNA molecules that are involved in posttranscriptional regulation of gene expression, whereas the pathophysiology of neuroblastoma tumor growth involves both upregulation of the protooncogenic miRNAs as well as downregulation of the tumor-suppresor ones. Comparison of the expression profiles of miRNAs in specific subtypes of neuroblastoma seems to be a useful tool adding to the classification of the diseases, and the assessment of the levels of specific miRNAs may be useful for estimation of the individual treatment response as well as prognosis of the patient. This paper provides the basic review of the studies focused on the role of miRNAs in pathogenesis of neuroblastoma and provides a survey of current/ possible use of these miRNAs in diagnostics, therapy or prognosis estimation in the neuroblastoma patients.

MicroRNAs are short non-coding RNAs involved in post-trascriptional regulation of gene expression. They can be found in various organisms including animals, plants and viruses and they play a key role in diverse biological processes, such as embryogenesis, differentiation and proliferation of cells, production of cytokines or apoptosis. Since the initial observation, more than 700 microRNAs have been identified in mammalian cells and up to one third of all protein-encoding genes is estimated to be regulated by these small molecules. In order to biological functions of these mRNA targets, it is apparent today, that altered microRNA expression can contribute not only to carcinogenesis but also to serious failure of the immune system. The aim of this review is to summarize the latest findings about the biogenesis and function of microRNAs and to refer on their role in the regulation of ontogenesis of immune system, haematopoiesis, immune responses and viral infections. Possible contribution of microRNAs to the therapy of viral infections is discussed.

Since many people all around the world are suffering from genetic disorders, modern therapeutic approaches are focused on the search of new pharmaceutical products. These products will be able to act on the gene level, more accurately on the nucleotide sequences themselves. RNA interference (RNAi) is an evolutionary conserved process that is caused by double stranded RNA (dsRNA). MicroRNA (miRNA) and small interfering RNA (siRNA) are the most important dsRNAs, which have been identified so far. Short (19-25 bp) non-coding dsRNAs are responsible for regulation of cellular development, heterochromatin formation and genomic stability in eukaryotes. Most importantly they are able to silence cognate genes. Therefore, they can provide new insights into the gene function and pathway analysis. Furthermore, they are believed to be new potential targets for diagnosis and therapeutics, especially for the treatment of genetic disorders, which can be caused by nucleotides insertions, deletions and translocations.

MicroRNAs (miRNAs) are large class of non-coding RNAs that post-transcriptionally regulate gene expression. Their ability of translational repression applied for example on oncogenes or tumor-suppressor genes indicates involvement of miRNAs in multi-step carcinogenesis. Evidences of miRNAs linkage to biological processes like apoptosis, proliferation, differentiation and cell survival are rapidly accumulating. Approximately 50% of miRNAs are located at fragile sites of chromosomes or regions known to be amplified or deleted in human cancer. That is why, non-coding miRNAs seem to be another level of genetic information which regulation is altered or lost during neoplastic growth. Expression profiles of miRNAs are successfully used for molecular classification, more exact diagnosis and prognosis of human cancers and reached analogical analytical characteristics like studies based on DNA micro-arrays technology and profiling of coding transcripts. In this review we attempt to introduce basic knowledge of miRNAs biogenesis and biological functions and in particular summarise reports focused on miRNAs in oncology research area.