microRNA clusters
Dotaz
Zobrazit nápovědu
Regulatory T cells (Tregs) are critical regulators of autoimmune diseases, including type 1 diabetes mellitus. It is hypothesised that Tregs' function can be influenced by changes in the expression of specific microRNAs (miRNAs). Thus, we performed miRNAs profiling in a population of Tregs separated from peripheral blood of five type 1 diabetic patients and six healthy donors. For more detailed molecular characterisation of Tregs, we additionally compared miRNAs expression profiles of Tregs and conventional T cells. Tregs were isolated according to CD3+, CD4+, CD25(hi)+ and CD127- by flow cytometry, and miRNA expression profiling was performed using TaqMan Array Human MicroRNA Panel-1 (384-well low density array). In Tregs of diabetic patients we found significantly increased expression of miRNA-510 (p=0.05) and decreased expression of both miRNA-342 (p<0.0001) and miRNA-191 (p=0.0079). When comparing Tregs and T cells, we revealed that Tregs had significant higher expression of miRNA-146a and lower expression of eight specific miRNAs (20b, 31, 99a, 100, 125b, 151, 335, and 365). To our knowledge, this is the first study demonstrating changes in miRNA expression profiles occurring in Tregs of T1D patients and a miRNAs signature of adult Tregs.
- MeSH
- diabetes mellitus 1. typu genetika krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- mladý dospělý MeSH
- regulační T-lymfocyty metabolismus MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů metody MeSH
- shluková analýza MeSH
- stanovení celkové genové exprese MeSH
- T-lymfocyty metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Stroke is the second leading cause of death worldwide. Understanding of gene expression dynamics could bring new approaches in diagnostics and therapy of stroke. Small noncoding molecules termed "microRNA" represent the most flexible network of gene expression regulators. METHOD: The aim of this review was to briefly describe the structure and function of microRNA and summarize the current knowledge about the involvement of microRNAs in the pathophysiology of ischemic and hemorrhagic stroke based on both experimental and clinical studies. RESULTS: Numerous profiling studies identified candidate microRNAs and partially described dynamics of their expression after the stroke. However, complex associations of specific microRNAs expression with main clinical characteristics and deeper insight into mechanisms of their regulatory functions are still missing. In this review, we put special emphasis on several microRNA clusters involved in neuroprotection (miR-124, miR-181, miR-21, miR-29, miR-210 and let7). Potential application of microRNAs as biomarkers and diagnostic or therapeutic targets was also discussed. CONCLUSION: Full understanding of the regulatory mechanisms of the microRNA networks represents a novel direction for stroke research. To date, we do not have effective tools to control pathophysiological processes associated with stroke. Thus the microRNAs have to be considered as a very promising target for future stroke therapies.
- MeSH
- biologické markery metabolismus MeSH
- cévní mozková příhoda genetika MeSH
- ischemie mozku genetika MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- regulace genové exprese genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Oct4-mediated reprogramming has recently become a novel tool for the generation of various cell types from differentiated somatic cells. Although molecular mechanisms underlying this process are unknown, it is well documented that cells over-expressing Oct4 undergo transition from differentiated state into plastic state. This transition is associated with the acquisition of stem cells properties leading to epigenetically "open" state that is permissive to cell fate switch upon external stimuli. In order to contribute to our understanding of molecular mechanisms driving this process, we characterised human fibroblasts over-expressing Oct4 and performed comprehensive small-RNAseq analysis. Our analyses revealed new interesting aspects of Oct4-mediated cell plasticity induction. Cells over-expressing Oct4 lose their cell identity demonstrated by down-regulation of fibroblast-specific genes and up-regulation of epithelial genes. Interestingly, this process is associated with microRNA expression profile that is similar to microRNA profiles typically found in pluripotent stem cells. We also provide extensive network of microRNA families and clusters allowing us to precisely determine the miRNAome associated with the acquisition of Oct4-induced transient plastic state. Our data expands current knowledge of microRNA and their implications in cell fate alterations and contributing to understanding molecular mechanisms underlying it.
- MeSH
- buněčné linie MeSH
- embryo savčí * MeSH
- fibroblasty cytologie metabolismus MeSH
- lidé MeSH
- mikro RNA * biosyntéza genetika MeSH
- oktamerní transkripční faktor 3 * biosyntéza genetika MeSH
- regulace genové exprese * MeSH
- techniky buněčného přeprogramování * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Kromě regulace genové exprese regulují krátké nekódující molekuly RNA (microR, miR) rychlost degradace a translace informační RNA (messenger RNA). Krátké nekódující molekuly miR vykazují vysokou expresi v kardiovaskulárním (KV) systému, což ukazuje na jejich významnou úlohu ve vaskulárním zdraví. Proces vzniku a rozvoje aterosklerózy je dáván do souvislosti s miR-221 a -222. Krátké nekódující molekuly miR-221/222 působí proti vzniku stenóz a mohou potenciálně sloužit jako marker remodelace myokardu. Přesto ještě potrvá dlouho, než bude možno považovat molekuly miR-221/222 jako možný cíl léčby. Identifikace, ověření a poznání funkcí genových cílů, všechny tyto procesy jsou nesmírně důležité.
In addition to regulating gene expression, microRNAs (MiRs) regulate messenger RNA degradation and translation rates. MiRs have a high expression in the cardiovascular (CV) system, indicating an important role in vascular health. The atherosclerotic process has been related to miRs-221 and -222. MiRs-221/222 possess anti-stenotic activity. MiR-221/222 may potentially serve as a marker for myocardial remodeling. There is still a long way yet before miRs-221/222 can be recognized as a potential therapeutic target. Identification, validation, and understanding of the function of gene targets are all critical.
MicroRNAs are small non-coding single-stranded RNA molecules regulating gene expression on a post-transcriptional level based on the seed sequence similarity. They are frequently clustered; thus, they are either simultaneously transcribed into a single polycistronic transcript or they may be transcribed independently. Importantly, microRNA families that contain the same seed region and thus target related signaling proteins, may be localized in one or more clusters, which are in a close relationship. MicroRNAs are involved in basic physiological processes, and their deregulation is associated with the origin of various pathologies, including solid tumors or hematologic malignancies. Recently, the interplay between the expression of microRNA clusters and families and epigenetic machinery was described, indicating aberrant DNA methylation or histone modifications as major mechanisms responsible for microRNA deregulation during cancerogenesis. In this review, the most studied microRNA clusters and families affected by hyper- or hypomethylation as well as by histone modifications are presented with the focus on particular mechanisms. Finally, the diagnostic and prognostic potential of microRNA clusters and families is discussed together with technologies currently used for epigenetic-based cancer therapies.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Incipient sympatric speciation in blind mole rat, Spalax galili, in Israel, caused by sharp ecological divergence of abutting chalk-basalt ecologies, has been proposed previously based on mitochondrial and whole-genome nuclear DNA. Here, we present new evidence, including transcriptome, DNA editing, microRNA, and codon usage, substantiating earlier evidence for adaptive divergence in the abutting chalk and basalt populations. Genetic divergence, based on the previous and new evidence, is ongoing despite restricted gene flow between the two populations. The principal component analysis, neighbor-joining tree, and genetic structure analysis of the transcriptome clearly show the clustered divergent two mole rat populations. Gene-expression level analysis indicates that the population transcriptome divergence is displayed not only by soil divergence but also by sex. Gene ontology enrichment of the differentially expressed genes from the two abutting soil populations highlights reproductive isolation. Alternative splicing variation of the two abutting soil populations displays two distinct splicing patterns. L-shaped FST distribution indicates that the two populations have undergone divergence with gene flow. Transcriptome divergent genes highlight neurogenetics and nutrition characterizing the chalk population, and energetics, metabolism, musculature, and sensory perception characterizing the abutting basalt population. Remarkably, microRNAs also display divergence between the two populations. The GC content is significantly higher in chalk than in basalt, and stress-response genes mostly prefer nonoptimal codons. The multiple lines of evidence of ecological-genomic and genetic divergence highlight that natural selection overrules the gene flow between the two abutting populations, substantiating the sharp ecological chalk-basalt divergence driving sympatric speciation.
- MeSH
- ekosystém MeSH
- mikro RNA metabolismus MeSH
- půda MeSH
- silikáty MeSH
- Spalax genetika metabolismus MeSH
- sympatrie * MeSH
- tok genů MeSH
- transkriptom * MeSH
- uhličitan vápenatý MeSH
- vznik druhů (genetika) * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Lenalidomide is a novel thalidomide analogue with immunomodulatory and antiangiogenic effects that has been successfully used for the treatment of low and intermediate-1 risk myelodysplastic syndromes (MDSs) with a del(5q) aberration. Because information about the influence of lenalidomide on the microRNA (miRNA) transcriptome is limited, we performed miRNA expression profiling of bone marrow CD34+ cells obtained from MDS patients with the del(5q) abnormality who had been subjected to lenalidomide treatment. To define differences in miRNA expression, we performed paired data analysis to compare the miRNA profiles of patients before and during lenalidomide treatment and those of healthy donors. The analysis showed that miRNAs clustering to the 14q32 region had a higher expression level in patient samples before treatment than in the healthy control samples, and this elevated expression was diminished following lenalidomide administration. Because some of the 14q32 miRNAs play important roles in hematopoiesis, stem cell differentiation, and apoptosis induction, the expression of this cluster may be associated with the pathophysiology of the disease.
- MeSH
- chromozomální delece MeSH
- imunologické faktory terapeutické užití MeSH
- inhibitory angiogeneze terapeutické užití MeSH
- lidé MeSH
- lidské chromozomy, pár 14 genetika MeSH
- lidské chromozomy, pár 5 genetika MeSH
- mikro RNA genetika MeSH
- myelodysplastické syndromy farmakoterapie genetika MeSH
- regulace genové exprese u nádorů MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- sekvenční delece MeSH
- stanovení celkové genové exprese MeSH
- studie případů a kontrol MeSH
- thalidomid analogy a deriváty terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
MicroRNAs (miRNAs) are small non-coding RNAs functioning as regulators of hematopoiesis. Their differential expression patterns have been linked with various pathological processes originating from hematopoietic stem cells (HSCs). However, limited information is available regarding the role of miRNAs in myelodysplastic syndrome (MDS). Using miRNA arrays, we measured expression of 1,145 miRNAs in CD34+ bone marrow cells obtained from 39 MDS and acute myeloid leukemia (AML) evolved from MDS patients, and compared them with those of six healthy donors. Differential miRNA expression was analyzed and a panel of upregulated (n=13) and downregulated (n=9) miRNAs were found (P<0.001) in MDS/AML patients. An increased expression of a large miRNA cluster mapped within the 14q32 locus was detected. Differences in miRNA expression of MDS subtypes showed a distinction between early and advanced MDS; an apparent dissimilarity was observed between RAEB-1 and RAEB-2 subtypes. In early MDS, we monitored upregulation of proapoptotic miR-34a, which may contribute to the increased apoptosis of HSCs. Patients with 5q deletion were characterized by decreased levels of miR-143(*) and miR-378 mapped within the commonly deleted region at 5q32. This is an early report describing differential expression in MDS CD34+ cells, likely reflecting their disease-specific regulation.
- MeSH
- akutní myeloidní leukemie metabolismus MeSH
- analýza rozptylu MeSH
- antigeny CD34 analýza imunologie MeSH
- apoptóza MeSH
- delece genu MeSH
- dospělí MeSH
- down regulace MeSH
- hematopoetické kmenové buňky cytologie imunologie MeSH
- hematopoéza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- mikročipová analýza MeSH
- mladý dospělý MeSH
- multigenová rodina MeSH
- myelodysplastické syndromy genetika patologie MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- up regulace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Primary tumor spread to the liver is the major cause of disease progression and death in patients with colorectal cancer (CRC). MicroRNAs (miRNAs) are small non-coding RNAs that are involved in cancer development and progression, but their role in metastasis has not been extensively investigated. MATERIALS AND METHODS: Firstly, expression profiling of 752 miRNAs in 20 primary tumors and their corresponding liver metastases was performed. Secondly, validation of the results was carried out on an independent cohort of 66 patients with metastatic CRC using reverse transcription-quantitative polymerase chain (RT-qPCR) reaction. RESULTS: In total, 33 miRNAs were found to be significantly deregulated in liver metastases compared to their primary tumors. Fifteen miRNAs were chosen for subsequent validation, which confirmed significantly reduced expression of miR-143, miR 10b, and miR-28-5p, and increased expression of miR 122, miR-122*, and miR 885-5p in the tissue of liver metastases. CONCLUSION: These results indicate that miRNAs could serve as new therapeutic targets in patients with metastatic CRC.
- MeSH
- celogenomová asociační studie * MeSH
- dospělí MeSH
- kolorektální nádory genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- nádory jater sekundární MeSH
- regulace genové exprese u nádorů MeSH
- reprodukovatelnost výsledků MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- shluková analýza MeSH
- stanovení celkové genové exprese * MeSH
- transkriptom MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
