• MeSH
• klinické laboratorní techniky MeSH
• molekulární biologie MeSH
• RNA MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Publikační typ
• kolektivní monografie

• MeSH
• molekulární biologie MeSH
• Publikační typ
• laboratorní příručky MeSH
• příručky MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biologie

OBJECTIVE: Mesial temporal lobe epilepsy (mTLE) is a severe neurological disorder characterized by recurrent seizures. mTLE is frequently accompanied by neurodegeneration in the hippocampus resulting in hippocampal sclerosis (HS), the most common morphological correlate of drug resistance in mTLE patients. Incomplete knowledge of pathological changes in mTLE+HS complicates its therapy. The pathological mechanism underlying mTLE+HS may involve abnormal gene expression regulation, including posttranscriptional networks involving microRNAs (miRNAs). miRNA expression deregulation has been reported in various disorders, including epilepsy. However, the miRNA profile of mTLE+HS is not completely known and needs to be addressed. METHODS: Here, we have focused on hippocampal miRNA profiling in 33 mTLE+HS patients and nine postmortem controls to reveal abnormally expressed miRNAs. In this study, we significantly reduced technology-related bias (the most common source of false positivity in miRNA profiling data) by combining two different miRNA profiling methods, namely next generation sequencing and miRNA-specific quantitative real-time polymerase chain reaction. RESULTS: These methods combined have identified and validated 20 miRNAs with altered expression in the human epileptic hippocampus; 19 miRNAs were up-regulated and one down-regulated in mTLE+HS patients. Nine of these miRNAs have not been previously associated with epilepsy, and 19 aberrantly expressed miRNAs potentially regulate the targets and pathways linked with epilepsy (such as potassium channels, γ-aminobutyric acid, neurotrophin signaling, and axon guidance). SIGNIFICANCE: This study extends current knowledge of miRNA-mediated gene expression regulation in mTLE+HS by identifying miRNAs with altered expression in mTLE+HS, including nine novel abnormally expressed miRNAs and their putative targets. These observations further encourage the potential of microRNA-based biomarkers or therapies.

• MeSH
• dospělí MeSH
• down regulace MeSH
• epilepsie temporálního laloku genetika   metabolismus   patologie   chirurgie   MeSH
• hipokampus metabolismus   patologie   chirurgie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• počítačová simulace MeSH
• regulace genové exprese * MeSH
• sekvenční analýza RNA MeSH
• skleróza MeSH
• stanovení celkové genové exprese MeSH
• upregulace MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Dendritic cells (DCs) belong to the immune system and are particularly studied for their potential to direct either an activated or tolerogenic immune response. The roles of microRNAs (miRNAs) in posttranscriptional gene expression regulation are being increasingly investigated. This study's aim is to evaluate the miRNAs' expression changes in prepared human immature (iDCs), activated (aDCs), and tolerogenic dendritic cells (tDCs). The dendritic cells were prepared using GM-CSF and IL-4 (iDC) and subsequently maturated by adding LPS and IFN-γ (aDC) or IL-10 and TGF-β (tDC). Surface markers, cytokine profiles, and miRNA profiles were evaluated in iDC, tDC, and aDC at 6 h and 24 h of maturation. We identified 4 miRNAs (miR-7, miR-9, miR-155 and miR-182), which were consistently overexpressed in aDC after 6 h and 24 h of maturation and 3 miRNAs (miR-17, miR-133b, and miR-203) and miR-23b cluster solely expressed in tDC. We found 5 miRNAs (miR-10a, miR-203, miR-210, miR-30a, and miR-449b) upregulated and 3 miRNAs downregulated (miR-134, miR-145, and miR-149) in both tDC and aDC. These results indicate that miRNAs are specifically modulated in human DC types. This work may contribute to identifying specific modulating miRNAs for aDC and tDC, which could in the future serve as therapeutic targets in the treatment of cancer and autoimmune diseases.

• MeSH
• dendritické buňky účinky léků   metabolismus   MeSH
• faktor stimulující granulocyto-makrofágové kolonie farmakologie   MeSH
• interleukin-10 farmakologie   MeSH
• interleukin-4 farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• mikro RNA genetika   MeSH
• průtoková cytometrie MeSH
• transformující růstový faktor beta farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The involvement of microRNAs (miRNAs) in orchestrating self-renewal and differentiation of stem cells has been revealed in a number of recent studies. And while in human pluripotent stem cells, miRNAs have been directly linked to the core pluripotency network, including the cell cycle regulation and the maintenance of the self-renewing capacity, their role in the onset of differentiation in other contexts, such as determination of neural cell fate, remains poorly described. To bridge this gap, we used three model cell types to study miRNA expression patterns: human embryonic stem cells (hESCs), hESCs-derived self-renewing neural stem cells (NSCs), and differentiating NSCs. The comprehensive miRNA profiling presented here reveals novel sets of miRNAs differentially expressed during human neural cell fate determination in vitro. Furthermore, we report a miRNA expression profile of self-renewing human NSCs, which has been lacking to this date. Our data also indicates that miRNA clusters enriched in NSCs share the target-determining seed sequence with cell cycle regulatory miRNAs expressed in pluripotent hESCs. Lastly, our mechanistic experiments confirmed that cluster miR-17-92, one of the NSCs-enriched clusters, is directly transcriptionally regulated by transcription factor c-MYC.

• MeSH
• buněčná diferenciace genetika   MeSH
• embryonální kmenové buňky MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• nervové kmenové buňky * metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Glioblastoma multiforme (GBM) is the most aggressive intracranial tumor characterized with infaust prognosis. Despite advances in neurosurgical and radiotherapeutic techniques and chemotherapy, the median overall survival ranges between 12-15 months from diagnosis. The main cause of treatment failure is considered the presence of tumor cells resistant to conventional therapy, mainly radiotherapy. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and have been repeatedly proven to play important roles in pathogenesis and biological features of many cancers, including GBM and its radioresistant phenotype. In our study, we established radioresistant cells from the commonly used human GBM cell lines T98G, U87MG and U251. Consequently, we performed global miRNA expression profiling in both radioresistant and parental cell lines and identified 113 miRNAs with significantly different expression (p<0.05) between these two groups (73 miRNAs were up-regulated, 40 miRNAs were down-regulated). Some of these miRNAs have been previously described in relation to ionizing radiation, and others were herein identified for the first time. We believe that after deeper functional investigation of identified miRNAs in relation to radioresistance, these miRNAs present potential predictive biomarkers or therapeutic targets in GBM.

• MeSH
• apoptóza MeSH
• fenotyp MeSH
• glioblastom genetika   patologie   MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory mozku genetika   patologie   MeSH
• prognóza MeSH
• proliferace buněk MeSH
• regulace genové exprese u nádorů * MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese MeSH
• tolerance záření genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• časná diagnóza MeSH
• diagnostické techniky molekulární MeSH
• exprese genu MeSH
• genom lidský MeSH
• lidé MeSH
• messenger RNA analýza   MeSH
• mikro RNA analýza   MeSH
• polymerázová řetězová reakce MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• recenze MeSH

MicroRNAs (miRNAs), important regulators of cellular processes, show specific expression signatures in different blood cell lineages and stages of hematopoietic stem cell (HSC) differentiation, indicating their role in the control of hematopoiesis. Because neonatal blood displays various features of immaturity, we might expect differential miRNA regulation. Herein, we determined miRNA expression profiles of umbilical cord blood (UCB) cell lineages and compared them to those of bone marrow (BM) and peripheral blood (PB) cell counterparts. Further, we determined mRNA expression profiles using whole-genome microarrays. An approach combining bioinformatic prediction of miRNA targets with mRNA expression profiling was used to search for putative targets of miRNAs with potential functions in UCB. We pointed out several differentially expressed miRNAs and associated their expression with the target transcript levels. miR-148a expression was suppressed in HSCs and its level inversely correlated with the previously verified target, DNA methyltransferase 3B, suggesting dependence of de novo DNA methylation in HSCs on miR-148a. Prolonged cell survival of UCB HSCs may be associated with low expression of miR-143 and miR-145 and up-regulation of their downstream targets (high expression of c-MYC and miR-17-92 and following repression of TGFBR2). In HSCs, we monitored significant up-regulation of eight miRNAs, which were previously verified as regulators of HOX genes. Further, miR-146b may be associated with immaturity of neonatal immune system because it is strongly up-regulated in UCB granulocytes and T lymphocytes compared to PB cell counterparts. Comparative analysis revealed 13 miRNAs significantly altered between UCB and BM CD34(+) cells. In UCB CD34(+) cells, we monitored up-regulation of miR-520h, promoting differentiation of HSCs into progenitor cells, and reduction of miR-214, whose expression might support HSC survival. In conclusion, UCB cells show specific miRNA expression patterns, indicating different regulation in these cells.

• MeSH
• antigeny CD34 metabolismus   MeSH
• buněčný rodokmen genetika   MeSH
• dospělí MeSH
• fetální krev cytologie   metabolismus   MeSH
• hematopoetické kmenové buňky metabolismus   MeSH
• krevní buňky metabolismus   fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• novorozenec MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• senioři MeSH
• shluková analýza MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• validační studie MeSH

Karcinom ovaria je nejzhoubnějším gynekologickým nádorem. Nejnovější výzkumy ukazují, že v ovariální karcinogenezi hrají významnou roli extraovariální tkáně. Přesto není přesná etiologie karcinomu ovaria známa a dosud neexistuje screeningový marker pro záchyt nemoci v časném stadiu. Velká pozornost současného výzkumu je věnována nekódujícím RNA, především mikroRNA. Tyto molekuly mohou regulovat expresi genů na posttranskripční úrovni a uplatňují se v řadě buněčných procesů. V karcinogenezi se mohou uplatňovat také jako regulační faktory, např. v roli tumor-supresorů i onkogenů. U karcinomu ovaria byly identifikovány profily exprese různých mikroRNA pro různé typy vzorků. V současnosti však neexistuje konsenzuální profil exprese mikroRNA, použitelný pro klinickou diagnostiku karcinomu ovaria. Diagnostický význam exprese mikroRNA v budoucnosti vzroste s rozvojem analýz neinvazivně odebíraného materiálu (např. moči, slin) a dalších analýz séra a krve. V tomto článku uvádíme přehled deregulovaných mikroRNA, identifikovaných v recentních výzkumech karcinomu ovaria, zahrnujících tkáně, exozomy, sérum a plnou krev, a také nalezených jako deregulované u recidivujících karcinomů ovaria. U některých mikroRNA jsou určité funkce částečně známy, ale u mnohých je objasnění jejich funkce v ovariální karcinogenezi otázkou pro budoucí výzkumy. MikroRNA tak mají velký potenciál stát na počátku nových diagnostických a terapeutických postupů u karcinomu ovaria i jiných nádorových onemocnění. Klíčová slova: karcinom ovaria – diagnostika karcinomu ovaria – mikroRNA – markery adenokarcinomu – adeno-karcinom

Epithelial ovarian cancer is the most fatal gynecologic cancer. Recent studies suggest an extraovarian origin for this disease. However, there is lack of information on exact etiology of ovarian cancer, and screening markers are also lacking. Non-coding RNA, particularly microRNAs are currently intensively investigated. They may be implicated in various cellular processes and regulate the gene expression at post-transcriptional level. In carcinogenesis, they may be involved as well, e.g. as tumor suppressors, or oncogenes. There have been identified expression profiles of microRNAs for various types of samples in ovarian cancer, however no expression profile is currently available for use in clinical diagnosis of ovarian cancer. Analyses of non-invasively collected material (e.g. urine, saliva) and further analyses of serum, or blood may provide basis for establishment of better diagnostic tools. We reviewed the studies on microRNAs shown to be deregulated in ovarian cancer, and coming from tumor tissues, plasma exosomes, serum, whole blood, and differing also between recurrent vs. primary ovarian cancer tissues. Function of particular microRNA is known partially only in several cases; however, for many microRNAs an elucidation of their functional role remains the goal for future investigations. MicroRNAs thus may stand at the beginning of novel diagnostic and therapeutic tools for ovarian cancer and other malignancies. Key words: ovarian cancer – diagnostics of ovarian cancer – microRNA – markers of adeno­carcinoma – adeno- ­carcinoma

• Klíčová slova
• markery adenokarcinomu, adenonokarcinom,
• MeSH
• exprese genu MeSH
• karcinom * diagnóza   klasifikace   MeSH
• mikro RNA * diagnostické užití   fyziologie   genetika   krev   MeSH
• nádorové biomarkery * MeSH
• nádory vaječníků * diagnóza   klasifikace   MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: Meningioma growth rates are highly variable, even within benign subgroups, with some remaining stable, whereas others grow rapidly. OBJECTIVE: To identify molecular-genetic markers for more accurate prediction of meningioma recurrence and better-targeted therapy. METHODS: Microarrays identified microRNA (miRNA) expression in primary and recurrent meningiomas of all World Health Organization (WHO) grades. Those found to be deregulated were further validated by quantitative real-time polymerase chain reaction in a cohort of 172 patients. Statistical analysis of the resulting dataset revealed predictors of meningioma recurrence. RESULTS: Adjusted and nonadjusted models of time to relapse identified the most significant prognosticators to be miR-15a-5p, miR-146a-5p, and miR-331-3p. The final validation phase proved the crucial significance of miR-146a-5p and miR-331-3p, and clinical factors such as type of resection (total or partial) and WHO grade in some selected models. Following stepwise selection in a multivariate model on an expanded cohort, the most predictive model was identified to be that which included lower miR-331-3p expression (hazard ratio [HR] 1.44; P < .001) and partial tumor resection (HR 3.90; P < .001). Moreover, in the subgroup of total resections, both miRNAs remained prognosticators in univariate models adjusted to the clinical factors. CONCLUSION: The proposed models might enable more accurate prediction of time to meningioma recurrence and thus determine optimal postoperative management. Moreover, combining this model with current knowledge of molecular processes underpinning recurrence could permit the identification of distinct meningioma subtypes and enable better-targeted therapies.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   patologie   MeSH
• meningeální nádory genetika   patologie   MeSH
• meningeom genetika   patologie   MeSH
• mikro RNA * genetika   MeSH
• nádorové biomarkery genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH